Search results for: insulin

Authors: Mohammad Soltani, Ayoub Saeidi, Nikoo Khosravi, Hanieh Nohbaradar, Seyedeh Parya Barzanjeh, Hassane Zouhal

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Exercise training and herbs supplement represent have role in the treatment for patients with type 2 diabetes (T2D). However, it is unclear combined effects of exercise training and herbs supplements on diabetic risk markers. This study aimed to determine the effect of 12 weeks of combined exercise and broccoli supplementation on decitin-1 and insulin resistance in men with type 2 diabetes. Forty-four type 2 diabetes men (age, 48.52 ± 4.36) were randomly allocated to training -supplement (TS, n = 11), training- placebo (TP, n = 11), supplement (S, n = 11) and control- placebo (CP, n = 11) groups. The combined exercise program included 12 weeks, three sessions per week, that each session contained 45 minutes of resistance training with intensity 60-70% of one maximal repetition and 30 minutes aerobic training (running) with intensity 60-70% of maximum heart rate. In addition supplement groups consumed 10 grams of Broccoli per day for 12 weeks. Plasma Decitin-1, HOMA-IR, Insulin, glucose and body composition were assessed before and after training. Plasma Dectin-1, HOMA-IR, glucose and BMI significantly decreased in TS, TP and S groups compared with CP group (P < .05). In addition Insulin and skeletal muscles mass showed significant increase in TS and TP groups compared with S and CP groups (P < .05). It is concluded that both combined exercise training (aerobic-resistance) or broccoli supplement can improve plasma Decitin-1 and insulin resistance in two diabetic patients however combine of exercise training and broccoli supplement have more effective on these markers.

Keywords: broccoli supplements, combined training, decitin-1, insulin resistance, type 2 diabetes

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Authors: Chun-Chin Huang

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Individuals with prediabetes increase the risk of developing type 2 diabetes. Exercise is a potent stimulator of skeletal muscle glucose uptake and thus good for maintaining glucose homeostasis. That could be a conducive method to improve blood glucose regulation and prevent type 2 diabetes without medication intake. The aim of this study was to summarize mechanisms of insulin resistance and investigate the beneficial effects of acute and chronic aerobic exercise on glycemic control in prediabetes and type 2 diabetes. Aerobic exercise regulates glucose homeostasis and reduces blood glucose, insulin concentrations. Therefore, the type of aerobic exercise brings positive effects to prediabetes and type 2 diabetes.

Keywords: insulin resistance, glucose sensitivity, impaired fasting glucose, impaired glucose tolerance

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Authors: Asieh Abbassi Daloii, Fatemeh Fani, Ahmad Abdi

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Objective: The aim of this study was to determine the effect of 8 weeks endurance training and L-NAME on apelin in adipose tissue, glucose and insulin in elderly male’s rats. Methods: For this purpose, 24 vistar elderly rats with average 20 months old purchased from Razi Institute and transferred to Research Center were randomly divided into four groups: 1. control, 2. training, 3.training and L-NAME and 4. L-NAME. Training protocol performed for 8 weeks and 5 days a week with 75-80 VO2 max. All rats were killed 72 hours after the final training session and after 24 hours of fasting adipose tissue samples were collected and kept in -80. Also, Data was analyzed with One way ANOVA and Tucky in p < 0/05. Results: The results showed that the inhibition of nitric oxide on apelin in adipose tissue of adult male rats after eight weeks of endurance training increased significantly compared to the control group (p < 0.00). Also, the results showed no significant difference between the levels of insulin and glucose groups. Conclusion: It is likely that the increased apelin in adipose tissue in mice independent of insulin and glucose.

Keywords: endurance training, L-NAME, apelin in adipose tissue, elderly male rats

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Authors: Rady A., Elsheshai A., Elsawy M., Nagui R.

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Background and Aim: Metabolic syndrome affect around 20% of general population , authors have incriminated antipsychotics as serious risk factor that may provoke such derangement. The aim of our study is to assess metabolic syndrome in patients presenting psychotic features (delusions and hallucinations) whether schizophrenia or mood disorder and compare results in terms of drug naïf, on medication and healthy control. Subjects and Methods: The study recruited 40 schizophrenic patients, half of them drug naïf and the other half on antipsychotics, 40 patients with mood disorder with psychotic features, half of them drug naïf and the other half on medication, 20 healthy control. Exclusion criteria were put in order to exclude patients having already endocrine or metabolic disorders that my interfere with results obtain to minimize confusion bias. Metabolic syndrome assessed by measuring parameters including weight, body mass index, waist circumference, triglyceride level, HDL, fasting glucose, fasting insulin and insulin resistance Results: No difference was found when comparing drug naïf to those on medication in both schizophrenic and psychotic mood disorder arms, schizophrenic patients whether on medication or drug naïf should difference with control group for fasting glucose, schizophrenic patients on medication also showed difference in insulin resistance compared to control group. On the other hand, patients with psychotic mood disorder whether drug naïf or on medication showed difference from control group for fasting insulin level. Those on medication also differed from control for insulin resistance Conclusion: Our study didn’t reveal difference in metabolic syndrome among patients with psychotic features whether on medication or drug naïf. Only patients with Psychotic features on medication showed insulin resistance. Schizophrenic patients drug naïf or on medication tend to show higher fasting glucose while psychotic mood disorder whether drug naïf or on medication tend to show higher fasting insulin. This study suggest that presence of psychotic features themselves regardless being on medication or not carries a risk for insulin resistance and metabolic syndrome. Limitation: This study is limited by number of participants and larger numbers in future studies should be included in order to extrapolate results. Cohort longitudinal studies are needed in order to evaluate such hypothesis.

Keywords: schizophrenia, metabolic syndrome, psychosis, insulin, resistance

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Authors: H. El-Messiry, M. El-Zainy, D. Ghazy

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Diabetes is a metabolic disease that results in a variety of oral health complications. Green tea is a natural antioxidant proved to have powerful effects against diabetes. The aim of this study was to compare between the effect of insulin and green tea on the Parotid gland of streptozotocin induced diabetic Albino rats by using light and transmission electron microscopy. Forty male Albino rats were divided into control group and diabetic groups. The diabetic group received a single injection of 40 mg/kg of streptozotocin intra-peritoneal under anesthesia and was further subdivided into three subgroups: The diabetic untreated subgroup which was untreated for two weeks, the insulin treated subgroup which has received insulin subcutaneously in a daily dose of 5 IU/kg body weight/day for two weeks and a green tea treated subgroup received a daily dose of 1 ml/ 100 gm body weight intragastrically for two weeks. Rats were terminated and parotid glands were dissected and processed for light and transmission electron microscopic examination. Histological examination of the diabetic untreated subgroup revealed acinar cells with pyknotic and hyperchromatic nuclei with cytoplasmic vacuolations. Ultrastructurally, acinar cells showed nuclear pleomorphism, dilated rough endoplasmic reticulum and swollen mitochondria with damaged cristae. Inflammatory cell infiltration was detected both histologically and ultrastructurally. Ducts showed signs of degeneration with loss of their normal outline and stagnated secretion within the lumen. However, insulin and green tea treated subgroups showed minimal degenerative damage and were almost similar to the control with minimal changes. Treatment of the parotid gland of the streptozotocin induced diabetic rats with GT was closely comparable to the traditional insulin therapy in reducing signs of histological and ultrastructural damage.

Keywords: diabetes, green tea, insulin, parotid

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Authors: Eric Beyegue, Boris Azantza, Judith Laure Ngondi, Julius E. Oben

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Background: Dietary supplement may potentially help to fight obesity and other metabolic disorders such as adipogenesis, insulin resistance, and inflammation. The present study aimed to test whether supplementation with African walnuts (Aw) could have an effect on adipogenesis and others dysfunctions associated with obesity in rats. Methods: Wistar rats were fed with standard diet (SD) or high-fat high-sucrose diet (HFS) and HFS with supplemented (HFS-Aw) for eight weeks. Results: HFS diet-induced body weight gain and increased fat mass compared to SD. In addition HFS-fed rats developed fasting hyperglycaemia and insulinaemia as well as insulin resistance. Aw supplementation in HFS rats had a protective effect against adipose tissues weigh gain but slightly against body weight gain and major study related disorders. This could be mainly due to decreased food intake dependently of effect in food intake in central nervous system, which decreased in HFS rats supplemented with African walnut compared to the HFS-diet group. Interestingly, African walnut supplementation induced a slight decrease of fasting glycaemia, insulinaemia and Nitric Oxide which could partially explain its minor protective effect against diet-induced insulin resistance. Additionally a decrease in hepatic TG and transaminases levels suggesting a protective effect against liver injury. Conclusion: Taken together these data suggested that supplementation of African walnut could be used to prevent adipose weight gain and related disorders on the other hand, minimally reduced insulin resistance.

Keywords: African walnut, dietary fiber, insulin resistance, oxidative stress

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Authors: R. P. Hewawasam, M. H. A. D. de Silva, M. A. G. Iresha

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Obesity is associated with an increased risk of developing insulin resistance. Insulin resistance often progresses to type-2 diabetes mellitus and is linked to a wide variety of other pathophysiological features including hypertension, hyperlipidemia, atherosclerosis (metabolic syndrome) and polycystic ovarian syndrome. Macrosomia is common in infants born to not only women with gestational diabetes mellitus but also non-diabetic obese women. During the past two decades, obesity in children and adolescents has risen significantly in Asian populations including Sri Lanka. There is increasing evidence to believe that infants who are born large for gestational age (LGA) are more likely to be obese in childhood. It is also established from previous studies that Asian populations have higher percentage body fat at a lower body mass index compared to Caucasians. High leptin levels in cord blood have been reported to correlate with fetal adiposity at birth. Previous studies have also shown that cord blood C-peptide and insulin levels are significantly and positively correlated with birth weight. Therefore, the objective of this preliminary study was to determine the relationship between parameters of fetal insulin resistance such as leptin, C-peptide and insulin and the birth weight of the newborn in a study population in Southern Sri Lanka. Umbilical cord blood was collected from 90 newborns and the concentration of insulin, leptin, and C-peptide were measured by ELISA technique. Birth weight, length, occipital frontal, chest, hip and calf circumferences of newborns were measured and characteristics of the mother such as age, height, weight before pregnancy and weight gain were collected. The relationship between insulin, leptin, C-peptide, and anthropometrics were assessed by Pearson’s correlation while the Mann-Whitney U test was used to assess the differences in cord blood leptin, C-peptide, and insulin levels between groups. A significant difference (p < 0.001) was observed between the insulin levels of infants born LGA (18.73 ± 0.64 µlU/ml) and AGA (13.08 ± 0.43 µlU/ml). Consistently, A significant increase in concentration (p < 0.001) was observed in C-peptide levels of infants born LGA (9.32 ± 0.77 ng/ml) compared to AGA (5.44 ± 0.19 ng/ml). Cord blood leptin concentration of LGA infants (12.67 ng/mL ± 1.62) was significantly higher (p < 0.001) compared to the AGA infants (7.10 ng/mL ± 0.97). Significant positive correlations (p < 0.05) were observed among cord leptin levels and the birth weight, pre-pregnancy maternal weight and BMI between the infants of AGA and LGA. Consistently, a significant positive correlation (p < 0.05) was observed between the birth weight and the C peptide concentration. Significantly high concentrations of leptin, C-peptide and insulin levels in the cord blood of LGA infants suggest that they may be involved in regulating fetal growth. Although previous studies suggest comparatively high levels of body fat in the Asian population, values obtained in this study are not significantly different from values previously reported from Caucasian populations. According to this preliminary study, maternal pre-pregnancy BMI and weight may contribute as significant indicators of cord blood parameters of insulin resistance and possibly the birth weight of the newborn.

Keywords: large for gestational age, leptin, C-peptide, insulin

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Authors: Ayman A. Al Hayek, Asirvatham A. Robert, Mohamed A. Al Dawish, Rim B. Braham, Hanouf S. Goudeh, Fahad S. Al Sabaan

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Introduction: The aim of this study was to explore the impact of insulin pump therapy on diabetes treatment satisfaction and glycemic control among patients with type 1 diabetes mellitus (T1DM) in Saudi Arabia. Methods: A 6-month, prospective study was conducted among 47 patients (aged17–24 years) with T1DM who attended the Insulin Pump Clinic at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between April 2014 and November 2014. The respondents were purposively and conveniently selected and were interviewed using the Arabic version of the Diabetes Treatment Satisfaction Questionnaire at baseline, 3, and 6 months. Demographics and clinical variables including hemoglobin A1c (HbA1c) were also collected. Results: The mean (±standard deviation) age of the study cohort was 19.1 ± 1.93 years. Seventeen patients were male (36.2%) and 30 were female (63.8%). Compared to baseline, significant positive differences were found in treatment satisfaction among female patients and patients with long-standing T1DM at 6 months. Frequency of hyperglycemia and hypoglycemia declined significantly in female patient’s at 6 months and in patients who had a shorter duration of T1DM. Furthermore, significant positive differences were found in HbA1c levels among female patients and among those who had a shorter duration of T1DM compared to baseline. Both female and male patients and those with a shorter duration of T1DM showed significant decline in insulin necessity at6months when compared to baseline. Conclusion: Although multiple daily injections is a feasible preference for insulin supply, insulin pumps should also be considered for patients with T1DM as it appears to increase patients’ treatment satisfaction, decrease the frequency of hypoglycemia, hyperglycemia, and reduce HbA1c levels.

Keywords: type 1 diabetes, insulin pump, Saudi Arabia, T1DM

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Authors: Javad Mohiti-Ardekani, Shabodin Asadii, Ali Moradi

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Introduction: Curcumin, the yellow pigment in turmeric, has been shown as an anti-diabetic agent for centuries but only in recent few years, its mechanism of action has been under investigation. Some studies showed that curcumin might exert its anti-diabetic effect via increasing glucose transporter isotype-4 (GLUT4) gene and glycoprotein contents in cells. To investigate this possibility, we investigate the effects of extract and commercial curcumin with and without insulin on GLUT4 translocation from intracellular compartments of nuclear or endoplasmic reticulum membranes (N/ER) into the cytoplasmic membrane (CM). Methods and Material: C2C12 myoblastic cell line were seeded in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After myotubes formation, 40 µmolar Extract and Commercial curcumin, with or without insulin as intervention, and as control 1 % DMSO were added for 3 h. Cells were washed and homogenized followed by ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection using semi-quantitative Western blotting. Data analysis was done by two independent samples t-test for comparison of mean ± SD of GLUT4 percent in categories. GLUT4 contents were higher in CM groups curcumin and curcumin with insulin in comparison to 1 % DMSO-treated myotubes control group. Results: As our results have shown extract and commercial curcumin induces GLUT4 translocation from intra-cell into cell surface. The results have also shown synergic effect of curcumin on translocation of GLUT4 from intra-cell into cell surface in the presence of 100 nm insulin. Discussion: We conclude that curcumin may be a choice of type-2 diabetes mellitus treatment because its extract and commercial enhances GLUT4 contents in CM where it facilitates glucose entrance into the cell. However, it is necessary to trace the signaling pathways which are activated by curcumin.

Keywords: Curcumin, insulin, Diabetes type-2, GLUT4

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Authors: Chaoge Wang, Xiquan Weng, Yan Meng, Wentao Lin

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Objective: Cold exposure and exercise serve as two physiological stimuli to glycolipid metabolism and insulin sensitivity. So far, it remains to be elucidated whether exercise plus cold exposure can produce an addictive effect on promoting glycolipid metabolism and insulin sensitivity. Methods: 64 SD rats were subjected to high-fat and high-sugar diets for 9-week and sucessfully to establish an obesity model. They were randomly divided into 8 groups: normal control group (NC), normal exercise group (NE), continuous cold control group (CC), continuous cold exercise group (CE), acute clod control group (AC), acute cold exercise group (AE), intermittent cold control group (IC) and intermittent cold exercise group (IE). For continuous cold exposure, the rats stayed in a cold environment all day; for acute cold exposure, the rats were exposed to cold for only 4h before the end of the experiment; for intermittent cold exposure, the rats were exposed to cold for 4h per day. The protocol for treadmill runnings were as follows: 25m/min (speed), 0°C (slope), 30 mins each time, an interval for 10 mins between two runnings, twice/two days, lasting for 5 weeks. Sampling were conducted on the 5th weekend. Blood lipids, free fatty acids, blood glucose (FBG), and serum insulin (FINS) were examined, and the insulin resistance index (HOMA-IR = FBG (mmol/L)×FINS(mIU/L)/22.5) was calculated. SPSS 22.0 was used for statistical analysis of the experimental results, and the ANOVA analysis was performed between groups (p < 0.05 was significant). Results: (1) Compared with the NC group, the FBG of the rats was significantly declined in the NE, CE, AC, AE, and IE groups (p < 0.05), the FINS of the rats was significantly declined in the AE group (p < 0.05), the HOMA-IR of the rats was significantly declined in the NE, CE, AC, AE and IE groups (p < 0.05). Compared with the NE group, the FBG of the rats was significantly declined in the CE, AE, and IE groups (p < 0.05), the FINS and HOMA-IR of the rats were significantly declined in the AE group (p < 0.05). (2) Compared with the NC group, the CHO, TG, LDL-C, and FFA of the rats were significantly declined in CE and IE groups (p < 0.05), the HDL-C of the rats was significantly higher in NE, CC, CE, AE, and IE groups (p < 0.05). Compared with the NE group, the HDL-C of the rats was significantly higher in the CE and IE groups (p < 0.05). Conclusions: Sedentariness or exercise in the acute cold doesn't make sense in the treatment of type 2 diabetes, which led to one-off increases of the body's insulin sensitivity. Exercise in the continuous and intermittent cold can effectively decline the FBG, TC, TG, LDL-C, and FFA levels and increase the HDL-C level and insulin sensitivity in obese rats. These results can impact the prevention and treatment of type 2 diabetes.

Keywords: cold, exercise, insulin sensitivity, obesity

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Authors: Sajjad Rezaei, Mahdieh Molanouri Shamsi, Azadeh Jamali

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Background and purpose: Surfactant protein D (SP-D) is a lung-specific protein that is detectable in human plasma. Effect of exercise training on SP-D levels as well as its relation to metabolic indices is not known. The present study then aimed to investigate the effects of 10 weeks of aerobic training on serum levels of SP-D and insulin resistance in women with type 2 diabetes. Materials and methods: Twenty-two overweight women with type 2 diabetes mellitus were recruited through deliberate sampling and randomly assigned to intervention and control groups (11 in each group). The intervention group underwent a progressive aerobic training program for 10 weeks, 3 days per week, 30-55 min/day at 50-75% heart rate reserve (HRR). Control group continued with its everyday routine. Blood samples were obtained before and after training for biochemical analysis. Within-group and between-group differences were analyzed with paired and independent t-tests in spss software, respectively, and the relation between variables was analyzed with Pearson’s correlation coefficient (all at P = 0.05). Results: Significant differences were observed between groups in leptin, glucose, waist circumference and VO2 max after training. SP-D was decreased and VO2 max was increased significantly in intervention group. However, no significant correlation was observed between SP-D and other variables. Conclusion: Since there was no corresponding decrease in insulin resistance with decreased levels of SP-D, it seems unlikely for SP-D to mediate the association between obesity and insulin resistance in type 2 diabetics.

Keywords: exercise training, SP-D, insulin resistance, type 2 diabetes

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Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and have been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. However, very little information is currently available for their mechanism. The prikly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, southwestern region of Korea, and used as a functional food. Present study investigated the effects of OFS on pancreatic β-cell function using pancreatic islet β cells (HIT cell). Alpha-glucosidase inhibition, glucose uptake, insulin secretion, insulin sensitivity, and pancreatic β cell proliferation were determined. The inhibitory effect of ethanol extract of OFS stem on α-glucosidase enzyme was measured in a cell free system. Glucose uptake was determined using fluorescent glucose analogue, 2-NBDG. Insulin secretion was measured by ELISA assay. Cell proliferation was measured by MTT assay. Ethanol extracts of OFS dose-dependently inhibited α-glucosidase activity as well as glucose uptake. Insulinotrophic effect of OFS extract was observed at high glucose media in pancreatic β-islet cells. Furthermore, pancreatic β cell regeneration was also observed.These results suggest that OFS mediates the antidiabetic activity mainly via α-glucosidase inhibition, glucose uptake, and improved insulin sensitivity.

Keywords: prickly pear cactus, Opuntia ficus-indica var. Saboten, pancreatic islet HIT cells, α-glucosidase, glucose uptake, insulinotrophic

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Authors: Andi Darmawan, Dewi Retno Sari Saputro, Purnami Widyaningsih

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Diabetes mellitus (DM) is a chronic disease in human that occurred if pancreas cannot produce enough of insulin hormone or the body uses ineffectively insulin hormone which causes increasing level of glucose in the blood, or it was called hyperglycemia. In Indonesia, DM is a serious disease on health because it can cause blindness, kidney disease, diabetic feet (gangrene), and stroke. The type of DM criteria can also be divided based on the main causes; they are DM type 1, type 2, and gestational. Diabetes type 1 or previously known as insulin-independent diabetes is due to a lack of production of insulin hormone. Diabetes type 2 or previously known as non-insulin dependent diabetes is due to ineffective use of insulin while gestational diabetes is a hyperglycemia that found during pregnancy. The most one type commonly found in patient is DM type 2. The main factors of this disease are genetic (A) and life style (E). Those disease with 2 factors can be constructed with additive genetic and unique environment (AE) model. In this article was discussed parameter estimation of AE model using Bayesian method and the inheritance character simulation on parent-offspring. On the AE model, there are response variable, predictor variables, and parameters were capable of representing the number of population on research. The population can be measured through a taken random sample. The response and predictor variables can be determined by sample while the parameters are unknown, so it was required to estimate the parameters based on the sample. Estimation of AE model parameters was obtained based on a joint posterior distribution. The simulation was conducted to get the value of genetic variance and life style variance. The results of simulation are 0.3600 for genetic variance and 0.0899 for life style variance. Therefore, the variance of genetic factor in DM type 2 is greater than life style.

Keywords: AE model, Bayesian method, diabetes mellitus type 2, genetic, life style

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Authors: M. H. A. D. de Silva, R. P. Hewawasam, M. A. G. Iresha

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Macrosomia is common in infants born to not only women diagnosed with gestational diabetes mellitus but also non-diabetic obese women. Maternal Body Mass Index (BMI) correlates with the incidence of large for gestational age infants. Obesity has reached epidemic levels in modern societies. During the past two decades, obesity in children and adolescents has risen significantly in Asian populations including Sri Lanka. There is increasing evidence to believe that infants who are born large for gestational age are more likely to be obese in childhood and adolescence and are at risk of cardiovascular and metabolic complications later in life. It is also established that Asians have lower skeletal muscle mass, low bone mineral content and excess body fat for a given BMI indicating a genetic predisposition in the occurrence of obesity. The objective of this study is to determine the effect of maternal weight, weight gain during pregnancy, c-peptide and insulin concentrations in the cord blood on the birth of appropriate for and large for gestational age infants in a tertiary care center in Southern Sri Lanka. Umbilical cord blood was collected from 90 newborns (Male 40, Female 50; gestational age 35-42 weeks) after double clamping the umbilical cord before separation of the placenta and the concentration of insulin and C-peptide were measured by ELISA technique. Anthropometric parameters of the newborn such as birth weight, length, ponderal index, occipital frontal, chest, hip and calf circumferences were measured, and characteristics of the mother were collected. The relationship between insulin, C-peptide and anthropometrics were assessed by Spearman correlation. The multiple logistic regression analysis examined influences of maternal weight, weight gain during pregnancy, C-peptide and insulin concentrations in cord blood as covariates on the birth of large for gestational age infants. A significant difference (P<0.001) was observed between the insulin levels of infants born large for gestational age (18.73 ± 0.52 µlU/ml) and appropriate for gestational age (13.08 ± 0.56 µlU/ml). Consistently, A significant decrease in concentration (41.68%, P<0.001) was observed between C-peptide levels of infants born large for gestational age and appropriate for gestational age. Cord blood insulin and C-peptide levels had a significant correlation with birth weight (r=0.35, P<0.05) of the newborn at delivery. Maternal weight and BMI which are indicators of maternal nutrition were proven to be directly correlated with birth weight and length. To our knowledge, this relationship was investigated for the first time in a Sri Lankan setting and was also evident in our results. This study confirmed the fact that insulin and C-peptide play a major role in regulating fetal growth. According to the results obtained in this study, we can suggest that the increased BMI of the mother has a direct influence on increased maternal insulin secretion, which may subsequently affect cord insulin and C-peptide levels and also birth weight of the infant.

Keywords: C-peptide, insulin, large for gestational age, maternal weight

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Authors: Masocorro Gawned, Stephen Myers, Guat Siew Chew

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Nuclear Receptors (NR) are a super family of transcription factors that play a major role in lipid and glucose metabolism in skeletal muscle. Recently, pharmacological evidence supports the view that stimulation of nuclear receptors alleviates Type 2 Diabetes (T2D). The orphan nuclear receptors (ONR) are members of the nuclear receptor (NR) superfamily whose ligands and physiological functions remain unknown. To date, no systematic studies have been carried out to screen for ONRs expressed in insulin resistant (IR) skeletal muscle cells. Therefore, in this study, we have established a model for IR by treating C2C12 skeletal muscle cells with insulin (10nM) for 48 hours. Western Blot analysis of phosphorylated AKT confirmed IR. Real-time quantitative polymerase chain reaction (qPCR) results highlighted key ONRs including NUR77 (NR4A1), NURR1 (NR4A2) and NOR1 (NR4A3) which have been associated with fatty acid oxidation regulation and glucose homeostasis. Increased mRNA expression levels of estrogen-related receptors (ERRs), REV-ERBα, NUR77, NURR1, NOR1, in insulin resistant C2C12 skeletal muscle cells, indicated that these ONRs could potentially play a pivotal regulatory role of insulin secretion in lipid metabolism. Taken together, this study has successfully contributed to the complete analysis of ONR in IR, and has filled in an important void in the study and treatment of T2D.

Keywords: type 2 diabetes, orphan nuclear receptors, transcription receptors, quantitative mRNA expression

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Authors: Adriana Muñoz-Talavera, Ana Rosa Rincón-Sánchez, Abraham Escobedo-Moratilla, María Cristina Islas-Carbajal, Miguel Ángel Gómez-Lim

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The highest rates of diabetes incidence and prevalence worldwide will increase the number of diabetic patients requiring insulin or insulin analogues. Then, current production systems would not be sufficient to meet the future market demands. Therefore, developing efficient expression systems for insulin and insulin analogues are needed. In addition, insulin analogues with better pharmacokinetics and pharmacodynamics properties and without mitogenic potential will be required. SCI-57 (single chain insulin-57) is an insulin analogue having 10 times greater affinity to the insulin receptor, higher resistance to thermal degradation than insulin, native mitogenicity and biological effect. Plants as expression platforms have been used to produce recombinant proteins because of their advantages such as cost-effectiveness, posttranslational modifications, absence of human pathogens and high quality. Immunoglobulin production with a yield of 50% has been achieved by transient expression in Nicotiana benthamiana (Nb). The aim of this study is to produce SCI-57 by transient expression in Nb. Methodology: DNA sequence encoding SCI-57 was cloned in pICH31070. This construction was introduced into Agrobacterium tumefaciens by electroporation. The resulting strain was used to infiltrate leaves of Nb. In order to isolate SCI-57, leaves from transformed plants were incubated 3 hours with the extraction buffer therefore filtrated to remove solid material. The resultant protein solution was subjected to anion exchange chromatography on an FPLC system and ultrafiltration to purify SCI-57. Detection of SCI-57 was made by electrophoresis pattern (SDS-PAGE). Protein band was digested with trypsin and the peptides were analyzed by Liquid chromatography tandem-mass spectrometry (LC-MS/MS). A purified protein sample (20µM) was analyzed by ESI-Q-TOF-MS to obtain the ionization pattern and the exact molecular weight determination. Chromatography pattern and impurities detection were performed using RP-HPLC using recombinant insulin as standard. The identity of the SCI-57 was confirmed by anti-insulin ELISA. The total soluble protein concentration was quantified by Bradford assay. Results: The expression cassette was verified by restriction mapping (5393 bp fragment). The SDS-PAGE of crude leaf extract (CLE) of transformed plants, revealed a protein of about 6.4 kDa, non-present in CLE of untransformed plants. The LC-MS/MS results displayed one peptide with a high score that matches SCI-57 amino acid sequence in the sample, confirming the identity of SCI-57. From the purified SCI-57 sample (PSCI-57) the most intense charge state was 1069 m/z (+6) on the displayed ionization pattern corresponding to the molecular weight of SCI-57 (6412.6554 Da). The RP-HPLC of the PSCI-57 shows the presence of a peak with similar retention time (rt) and UV spectroscopic profile to the insulin standard (SCI-57 rt=12.96 and insulin rt=12.70 min). The collected SCI-57 peak had ELISA signal. The total protein amount in CLE from transformed plants was higher compared to untransformed plants. Conclusions: Our results suggest the feasibility to produce insulin analogue SCI-57 by transient expression in Nicotiana benthamiana. Further work is being undertaken to evaluate the biological activity by glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes.

Keywords: insulin analogue, mass spectrometry, Nicotiana benthamiana, transient expression

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Authors: T. Mahesh, M. K. Samanta

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Antibody dug conjugate (ADC’s) concept is a less explored and more trustable for the treatment of Type 1 diabetes (T1D). T1D is thought to arise from selective immunologically mediated destruction of the insulin- producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. It is evident that type 1 diabetes can be conquered, by 1) to stop immune destruction of βcells, 2) to replace or regenerate β-cells, and 3) to preserve β-cell function and mass. Many studies found that the regulatory T cells (Tregs) are crucial for the maintenance of immunological tolerance. Immune tolerance is liable for the activation of the Th1 response. The important role of Th1 response in pathology of T1D entails the depletion of CD4+ T cells, which initiated the use of anti-CD4 monoclonal antibodies (mAbs) against CD4+ T cells to interfere with induction of T1D.Insulin is regulated by Glucagon-Like Peptide-1 hormone (GLP-1) which also stimulates β-cells proliferation as the half-life of GLP-1 harmone is less due to rapid degradation by DPP-IV enzyme an alternative DPP-IV-inhibitors can increase the half-life of GLP-1 through which it conquers the replacement and reserve β-cells mass. Thus in the present study Anti-CD4 mAb was conjugated with Sitagliptin which is a DPP-IV inhibitor Drug loaded in Nanoparticles through Sulfo-MBS cross-linkers. The above study can be an effective approach for treatment to overcome the Passive subcutaneous insulin therapy.

Keywords: antibody drug conjugates, anti-CD4 Mab, DPP IV inhibitors, GLP-1

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Authors: Amal Abo El-Maaty, Amira Mohamed, Nashwa Abu-Aita, Hisham Morgan

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For estimating markers of overweight or obesity of brood mares used for riding and training, 17 mares of different body conditions were subjected to blood sampling and ultrasound examination to measure rump fat thickness and monitor ovulation for six consecutive weeks. Also length (L), heart girth (G) and withers height (H) were measured to estimate body weight (BW), body fat %, body fat mass (BFM) and body mass index (BMI). Mares were classified into three groups according to both body condition score (BCS) and rump back fat (BF). Overweight mares (O) were having BCS > 7 and BF thickness >7mm, moderate body condition (M) mares were having BCS >3and ≤7and BF <3and <7mm, and emaciated mares (E) were having BCS ≤3 and BF ≤3mm. glucose, triglycerides, nitric oxide, ovarian, thyroid, insulin, insulin like growth factor-I (IGF-1), and leptin hormones were measured. Results revealed that BCS, G, L, L*G*H, BW, BF, fat %, BFM were significantly (P<0.0001) decreasing linearly from O to E. T4 concentrations of E were significantly high (P=0.04) compared to M and O but T3 concentrations tended to decrease in E (P>0.05). Insulin and IGF-1 concentrations tended to be high in O (P>0.05) and decrease with the decrease of body condition. M had (P=0.007) the highest leptin, but E mares had the lowest P4 concentrations (P=0.01). Concentrations of glucose and NO decreased with the decrease of BCS and BF but triglycerides of O were insignificantly high. In conclusion, exercise could prevent the development of metabolic syndrome in horses and back fat and morphometric measurements were the easiest and simple assessment of overweight and deviation to obesity.

Keywords: body condition score, insulin, leptin, mares, rump fat

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Authors: Nafiseh Mollaei, Reihaneh Kardehi Moghaddam

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In case of Diabetes Mellitus the controlling of insulin is very difficult. This illness is an incurable disease affecting millions of people worldwide. Glucose is a sugar which provides energy to the cells. Insulin is a hormone which supports the absorption of glucose. Fuzzy control strategy is attractive for glucose control because it mimics the first and second phase responses that the pancreas beta cells use to control glucose. We propose two control algorithms a type-1 fuzzy controller and an interval type-2 fuzzy method for the insulin infusion. The closed loop system has been simulated for different patients with different parameters, in present of the food intake disturbance and it has been shown that the blood glucose concentrations at a normoglycemic level of 110 mg/dl in the reasonable amount of time. This paper deals with type 1 diabetes as a nonlinear model, which has been simulated in MATLAB-SIMULINK environment. The novel model, termed the Augmented Minimal Model is used in the simulations. There are some uncertainties in this model due to factors such as blood glucose, daily meals or sudden stress. In addition to eliminate the effects of uncertainty, different control methods may be utilized. In this article, fuzzy controller performance were assessed in terms of its ability to track a normoglycemic set point (110 mg/dl) in response to a [0-10] g meal disturbance. Finally, the development reported in this paper is supposed to simplify the insulin delivery, so increasing the quality of life of the patient.

Keywords: interval type-2, fuzzy controller, minimal augmented model, uncertainty

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Authors: Pramod Somvanshi, Manu Tomar, K. V. Venkatesh

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Insulin and glucagon are responsible for homeostasis of key plasma metabolites like glucose, amino acids and fatty acids in the blood plasma. These hormones act antagonistically to each other during the secretion and signaling stages. In the present work, we analyze the effect of macronutrients on the response from integrated insulin and glucagon signaling pathways. The insulin and glucagon pathways are connected by DAG (a calcium signaling component which is part of the glucagon signaling module) which activates PKC and inhibits IRS (insulin signaling component) constituting a crosstalk. AKT (insulin signaling component) inhibits cAMP (glucagon signaling component) through PDE3 forming the other crosstalk between the two signaling pathways. Physiological level of anabolism and catabolism is captured through a metric quantified by the activity levels of AKT and PKA in their phosphorylated states, which represent the insulin and glucagon signaling endpoints, respectively. Under resting and starving conditions, the phosphorylation metric represents homeostasis indicating a balance between the anabolic and catabolic activities in the tissues. The steady state analysis of the integrated network demonstrates the presence of a bistable response in the phosphorylation metric with respect to input plasma glucose levels. This indicates that two steady state conditions (one in the homeostatic zone and other in the anabolic zone) are possible for a given glucose concentration depending on the ON or OFF path. When glucose levels rise above normal, during post-meal conditions, the bistability is observed in the anabolic space denoting the dominance of the glycogenesis in liver. For glucose concentrations lower than the physiological levels, while exercising, metabolic response lies in the catabolic space denoting the prevalence of glycogenolysis in liver. The non-linear positive feedback of AKT on IRS in insulin signaling module of the network is the main cause of the bistable response. The span of bistability in the phosphorylation metric increases as plasma fatty acid and amino acid levels rise and eventually the response turns monostable and catabolic representing diabetic conditions. In the case of high fat or protein diet, fatty acids and amino acids have an inhibitory effect on the insulin signaling pathway by increasing the serine phosphorylation of IRS protein via the activation of PKC and S6K, respectively. Similar analysis was also performed with respect to input amino acid and fatty acid levels. This emergent property of bistability in the integrated network helps us understand why it becomes extremely difficult to treat obesity and diabetes when blood glucose level rises beyond a certain value.

Keywords: bistability, diabetes, feedback and crosstalk, obesity

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Authors: Purwati, Sony Wibisono, Ari Sutjahjo, Askandar T. J., Fedik A. Rantam

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Diabetes mellitus type 2 (T2DM), also known as hyperglycemia, results from insulin resistance and relative insulin deficiency. Diabetes mellitus is the main cause of premature death, particularly among individuals under the age of 70 years old. Mesenchymal stem cells (MSCs) can release bioactive molecules that promote tissue repair and regeneration. Hence, in this research, we evaluated the potential of autologous adipose-derived mesenchymal stem cells (AD-MSCs) in 40 patients of phase I clinical trial in T2DM with various ages between 30-79 years. AD-MSCs are transferred through catheterization. MSCs were validated by measures of CD105+ and CD34- expression. The result showed that after AD-MSCs transplantation, blood glucose levels (fasting and 2-hour postprandial) and insulin levels were significantly decreasing. Besides that, the level of HbA1c significantly decreased after three months of AD-MSCs injection and increasing level of c-peptide after injection. Thus, we conclude that AD-MSCs injection has the potential for T2DM therapy.

Keywords: glucose, hyperglycemia, MSCs, T2DM

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Authors: Orkide Donma, Mustafa M. Donma

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Obesity, a disease associated with a low-grade inflammation, is a risk factor for the development of metabolic syndrome (MetS). So far, MetS risk factors such as parameters related to glucose and lipid metabolisms as well as blood pressure were considered for the evaluation of this disease. There are still some ambiguities related to the characteristic features of MetS observed particularly in pediatric population. Hormonal imbalance is also important, and quite a lot information exists about the behaviour of some hormones in adults. However, the hormonal profiles in pediatric metabolism have not been cleared yet. The aim of this study is to investigate the profiles of cortisol, insulin, and thyroid hormones in children with MetS. The study population was composed of morbid obese (MO) children without (Group 1) and with (Group 2) MetS components. WHO BMI-for age and sex percentiles were used for the classification of obesity. The values above 99 percentile were defined as morbid obesity. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Anthropometric measurements were performed. Ratios as well as obesity indices were calculated. Insulin, cortisol, thyroid stimulating hormone (TSH), free T₃ and free T₄ analyses were performed by electrochemiluminescence immunoassay. Data were evaluated by statistical package for social sciences program. p<0.05 was accepted as the degree for statistical significance. The mean ages±SD values of Group 1 and Group 2 were 9.9±3.1 years and 10.8±3.2 years, respectively. Body mass index (BMI) values were calculated as 27.4±5.9 kg/m² and 30.6±8.1 kg/m², successively. There were no statistically significant differences between the ages and BMI values of the groups. Insulin levels were statistically significantly increased in MetS in comparison with the levels measured in MO children. There was not any difference between MO children and those with MetS in terms of cortisol, T₃, T₄ and TSH. However, T₄ levels were positively correlated with cortisol and negatively correlated with insulin. None of these correlations were observed in MO children. Cortisol levels in both MO as well as MetS group were significantly correlated. Cortisol, insulin, and thyroid hormones are essential for life. Cortisol, called the control system for hormones, orchestrates the performance of other key hormones. It seems to establish a connection between hormone imbalance and inflammation. During an inflammatory state, more cortisol is produced to fight inflammation. High cortisol levels prevent the conversion of the inactive form of the thyroid hormone T₄ into active form T₃. Insulin is reduced due to low thyroid hormone. T₃, which is essential for blood sugar control- requires cortisol levels within the normal range. Positive association of T₄ with cortisol and negative association of it with insulin are the indicators of such a delicate balance among these hormones also in children with MetS.

Keywords: children, cortisol, insulin, metabolic syndrome, thyroid hormones

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Authors: Hitoshi Minakuchi, Izumi Takei, Shu Wakino, Koichi Hayashi, Hiroshi Itoh

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Objectives: Among type 2 diabetics, patients with CKD(chronic kidney disease), insulin resistance, impaired glyconeogenesis in kidney and reduced degradation of insulin are recognized, and we observed different fluctuational patterns of blood sugar between CKD patients and non-CKD patients. On the other hand, non-dipper type blood pressure change is the risk of organ damage and mortality. We performed cross-sectional study to elucidate the characteristic of the fluctuation of blood glucose and blood pressure at insulin-treated diabetic patients with chronic kidney disease. Methods: From March 2011 to April 2013, at the Ichikawa General Hospital of Tokyo Dental College, we recruited 20 outpatients. All participants are insulin-treated type 2 diabetes with CKD. We collected serum samples, urine samples for several hormone measurements, and performed CGMS(Continuous glucose measurement system), ABPM (ambulatory blood pressure monitoring), brain computed tomography, carotid artery thickness, ankle brachial index, PWV, CVR-R, and analyzed these data statistically. Results: Among all 20 participants, hypoglycemia was decided blood glucose 70mg/dl by CGMS of 9 participants (45.0%). The event of hypoglycemia was recognized lower eGFR (29.8±6.2ml/min：41.3±8.5ml/min, P<0.05), lower HbA1c (6.44±0.57%：7.53±0.49%), higher PWV (1858±97.3cm/s：1665±109.2cm/s), higher serum glucagon (194.2±34.8pg/ml：117.0±37.1pg/ml), higher free cortisol of urine (53.8±12.8μg/day：34.8±7.1μg/day), and higher metanephrin of urine (0.162±0.031mg/day：0.076±0.029mg/day). Non-dipper type blood pressure change in ABPM was detected 8 among 9 participants with hypoglycemia (88.9%), 4 among 11 participants (36.4%) without hypoglycemia. Multiplex logistic-regression analysis revealed that the event of hypoglycemia is the independent factor of non-dipper type blood pressure change. Conclusions: Among insulin-treated type 2 diabetic patients with CKD, the events of hypoglycemia were frequently detected, and can associate with the organ derangements through the medium of non-dipper type blood pressure change.

Keywords: chronic kidney disease, hypoglycemia, non-dipper type blood pressure change, diabetic patients

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Authors: A. Alhusban, M. Alqawasmeh, F. Alfawares

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Introduction: Diabetes is a chronic health problem and a major risk factor of stroke. A number of therapeutic modalities exist for diabetes management. It’s still unknown whether the different oral hypoglycemic agents would ameliorate the detrimental effect of diabetes on stroke severity. The objective of this work is to assess the effect of pretreatment with oral hypoglycemic agents, insulin and their combination on stroke severity at presentation. Patients and Methods: Patients admitted to the King Abdullah University Hospital (KAUH)-Jordan with ischemic stroke between January 2015 and December 2016 were evaluated and their comorbid diseases, treatment on admission and their neurologic severity was assessed using the National Institute of Health Stroke Scale (NIHSS) were documented. Stroke severity was compared for non-diabetic patients and diabetic patients treated with different antidiabetic agents. Results: Data from 324 patients with acute stroke was documented. The median age of participants was 69 years. Diabetes was documented in about 50% of the patients. Multinomial regression analysis identified diabetes treatment status as an independent predictor of neurological severity of stroke (p=0.032). Patients treated with oral hypoglycemic agents had a significantly lower NIHSS as compared to nondiabetic patients and insulin treated patients (p < 0.02). The positive effect of oral hypoglycemic agents was blunted by insulin co-treatment. Insulin did not alter the severity of stroke as compared to non-diabetics. Conclusion: Oral hypoglycemic agents may reduce the severity of neurologic deficit of ischemic stroke and may have neuroprotective effect.

Keywords: diabetes, stroke, neuroprotection, oral hypoglycemic agents

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Authors: Chin-Tsu Ma, Yi-Jhen Wu, Hsia Ying Cheng, Han Hsiang Huang, Shyh Ming Kuo

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The use of specific molecules including nutrients and pharmacological agents has been tried in modulation of stem cells differentiation (MSCs) to insulin producing cells. The aim of this study is to investigate the ability of nano collagen molecules (nutrient or scaffold) to enhance the MSCs differentiation into insulin-producing cells in combination with nicotinamide and exendin-4 (pharmacological agents) in vitro and in vivo. The results demonstrated that the cells exhibit morphologically islet-like clusters after treatment with nano collagen molecules, nicotinamide and exendin-4. MSCs extra treated with nano collagen molecules showed significant increases in Nkx6.1 and insulin mRNA expression at 14-d and 21-d culture compared with those merely treated with nicotinamide and exendin-4. Early 7-day elevation in PDX-1 mRNA expression was observed. Furthermore, the MSCs exposed to nano collagen molecules produced the highest secretion of insulin (p ＜ 0.05). Type-2 diabetes induced by high-fat diet and low dose of streptozotocin in rat model was built in this study. This rat exhibited higher food intake, water intake, lower glucose tolerance, lower-insulin tolerance, and higher HbA1C (significant increases, p ＜ 0.01) as compared with the normal rat that demonstrated the model of type-2 diabetes was successfully built. Biopsy examinations also showed that obvious destruction of islet. After injection of differentiated MSCs into the destructed pancreas of diabetes rat, more regenerated islet were observed at the rats that treated with nano collagen molecules and exhibited much lower HbA1C as compared with the normal rat and diabetes rat after 4 weeks (significant deceases, p ＜ 0.001). These results indicate that the culturing MSCs with nano collagen molecules, nicotinamide, and exendin-4 are beneficial for MSCs differentiation into islet-like cells. These nano collagen molecules may lead to alternations or up-regulation of gene expression and influence the differentiated outcomes induced by nicotinamide and exendin-4.

Keywords: nano collagen molecules, nicotinamide, MSCs, diabetes

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Authors: Christine Y. Yeh, Brian D. Piening, Sarah M. Totten, Kimberly Kukurba, Wenyu Zhou, Kevin P. F. Contrepois, Gucci J. Gu, Sharon Pitteri, Michael Snyder

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Three million deaths worldwide are attributed to obesity. However, the biomolecular mechanisms that describe the link between adiposity and subsequent disease states are poorly understood. Insulin resistance characterizes approximately half of obese individuals and is a major cause of obesity-mediated diseases such as Type II diabetes, hypertension and other cardiovascular diseases. This study makes use of longitudinal quantitative and high-throughput multi-omics (genomics, epigenomics, transcriptomics, glycoproteomics etc.) methodologies on blood samples to develop multigenic and multi-analyte signatures associated with weight gain and insulin resistance. Participants of this study underwent a 30-day period of weight gain via excessive caloric intake followed by a 60-day period of restricted dieting and return to baseline weight. Blood samples were taken at three different time points per patient: baseline, peak-weight and post weight loss. Patients were characterized as either insulin resistant (IR) or insulin sensitive (IS) before having their samples processed via longitudinal multi-omic technologies. This comparative study revealed a wealth of biomolecular changes associated with weight gain after using methods in machine learning, clustering, network analysis etc. Pathways of interest included those involved in lipid remodeling, acute inflammatory response and glucose metabolism. Some of these biomolecules returned to baseline levels as the patient returned to normal weight whilst some remained elevated. IR patients exhibited key differences in inflammatory response regulation in comparison to IS patients at all time points. These signatures suggest differential metabolism and inflammatory pathways between IR and IS patients. Biomolecular differences associated with weight gain and insulin resistance were identified on various levels: in gene expression, epigenetic change, transcriptional regulation and glycosylation. This study was not only able to contribute to new biology that could be of use in preventing or predicting obesity-mediated diseases, but also matured novel biomedical informatics technologies to produce and process data on many comprehensive omics levels.

Keywords: insulin resistance, multi-omics, next generation sequencing, proteogenomics, type ii diabetes

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Authors: Rukia Yosuf

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Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.

Keywords: diabetes, kidney disease, nephrology, prediabetes

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Authors: Maha Azzam, Mahmoud Gabr, Mahmoud Zakaria, Ayman Refaie, Amani Ismail, Sherry Khater, Sylvia Ashamallah, Mohamed Ghoniem

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Evidence was provided that human bone marrow-derived mesenhymal stem cells (HBM-MSCs) could be differentiated to form insulin-producing cells (IPCs). Transplantation of these cells was able to cure chemically-induced diabetes in nude mice. The efficacy of these cells to control diabetes in large animals was carried out to evaluate the sufficient number of cells needed/Kg body weight and to determine the functional longevity in vivo. Materials/Methods: Ten male mongrel dogs weighing 15-20 Kg were used in this study. Diabetes was chemically-induced in 7 dogs by a mixture of alloxan and streptozotocin. Three non-diabetic served as normal controls. Differentiated HBM-MSCs (5 million/Kg) were encapsulated in theracyte capsules and transplanted beneath the rectus sheath. Each dog received 2 capsules. One dog died 4 days postoperative from inhalation pneumonia. The remaining 6 dogs were followed up for 6-18 months. Results: Four dogs became normoglycemic within 6-8 weeks with normal glucose tolerance curves providing evidence that the transplanted cells were glucose-sensitive and insulin-responsive. In the remaining 2 dogs, fasting blood glucose was reduced but did not reach euglycemic levels. The sera of all transplanted dogs contained human insulin and c-peptide but negligible levels of canine insulin. When the HBM-MSCs loaded capsules were removed, rapid return of diabetic state was noted. The harvested capsules were examined by immunofluorescence. IPCs were seen and co-expression of with c-peptide was confirmed. Furthermore, all the pancreatic endocrine genes were expressed by the transplanted cells. Conclusions: This study provided evidence that theracyte capsules could protect the xenogenic HBM-MSCs from the host immune response. This is an important issue when clinical stem cell therapy is considered for definitive treatment for T1DM.

Keywords: diabetes, mesenchymal stem cells, dogs, Insulin-producing cells

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Authors: Mesih Kocamuftuoglu, Gonca Ozan, Enver Ozan, Nalan Kaya, Sema Temizer Ozan

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Metabolic Syndrome, one of the common metabolic disorder, occurs with co-development of insulin resistance, obesity, dislipidemia and hypertension problems. Insulin resistance appears to play a pathogenic role in the metabolic syndrome. Also, there is a relationship between insulin resistance and infertility as known. Turmeric (Curcuma longa L.) a polyphenolic chemical is widely used for its coloring, flavoring, and medicinal properties, and exhibits a strong antioxidant activity. In this study, we assess the effects of turmeric on rat uterine tissue in metabolic syndrome model induced by high fructose diet. Thirty-two adult female Wistar rats weighing 220±20 g were randomly divided into four groups (n=8) as follows; control, fructose, turmeric, and fructose plus turmeric. Metabolic syndrome was induced by fructose solution 20% (w/v) in tap water, and turmeric (C.Longa) administered at the dose of 80 mg/kg body weight every other day by oral gavage. After the experimental period of 8 weeks, rats were decapitated, serum and uterine tissues were removed. Serum lipid profile, glucose, insülin levels were measured. Uterine tissues were fixed for histological analyzes. The uterine tissue sections were stained with hematoxylin-eosin (H & E) stain, then examined and photographed on a light microscope (Novel N-800Mx20). As a result, fructose consumption effected serum lipids, insulin levels, and insulin resistance significantly. Endometrium and myometrium layers were observed in normal structure in control group of uterine tissues. Perivascular edema, peri glandular fibrosis, and inflammatory cell increase were detected in fructose group. Sections of the fructose plus turmeric group showed a significant improvement in findings when compared to the fructose group. Turmeric group cell structures were observed similar with the control group. These results demonstrated that high-fructose consumption could change the structure of the uterine tissue. On the other hand, turmeric administration has beneficial effects on uterine tissue at that dose and duration when administered with fructose.

Keywords: metabolic syndrome, rat, turmeric, uterus

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Authors: Xin Li, Yan-Rong Guo, Jin-Fang Lin, Yi Feng, Håkan Billig, Ruijin Shao

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Background: Young women with polycystic ovary syndrome (PCOS) have a high risk of developing endometrial carcinoma. There is a need for the development of new medical therapies that can reduce the need for surgical intervention so as to preserve the fertility of these patients. The aim of the study was to describe and discuss cases of PCOS and insulin resistance (IR) women with early endometrial carcinoma while being co-treated with Diane-35 and metformin. Methods: Five PCOS-IR women who were scheduled for diagnosis and therapy for early endometrial carcinoma were recruited. The hospital records and endometrial pathology reports were reviewed. All patients were co-treated with Diane-35 and metformin for 6 months to reverse the endometrial carcinoma and preserve their fertility. Before, during, and after treatment, endometrial biopsies and blood samples were obtained and oral glucose tolerance tests were performed. Endometrial pathology was evaluated. Body weight (BW), body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHBG), free androgen index (FAI), insulin area under curve (IAUC), and homeostasis model assessment of insulin resistance (HOMA-IR) were determined. Results: Clinical stage 1a, low grade endometrial carcinoma was confirmed before treatment. After 6 months of co-treatment, all patients showed normal epithelia. No evidence of atypical hyperplasia or endometrial carcinoma was found. Co-treatment resulted in significant decreases in BW, BMI, TT, FAI, IAUC, and HOMA-IR in parallel with a significant increase in SHBG. There were no differences in the FSH and LH levels after co-treatment. Conclusions: Combined treatment with Diane-35 and metformin has the potential to revert the endometrial carcinoma into normal endometrial cells in PCOS-IR women. The cellular and molecular mechanisms behind this effect merit further investigation.

Keywords: PCOS, progesterone resistance, insulin resistance, steroid hormone receptors, endometrial carcinoma

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