Search results for: insulin secretion

Authors: Hani M. M. Alothaid, Louise Robson, Richmond Muimo

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This study will investigate cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) dependent calcineurin (Cn), known as protein phosphatase 2 B (PP2B) as well, regulation of chloride ion (Cl⁻) secretion and the release of pro-inflammatory molecules in immune cells such as cytokines. THP-1-derived monocytes, primary human monocytes and the bronchial epithelial cell line (16HBE14o-) were used in this study. The 16HBE14o- cells were chosen as positive control. Hence, to further confirm the expression of cystic fibrosis transmembrane conductance regulator (CFTR), calcium binding protein (S100A10), annexin A2 (AnxA2) and calcineurin A subunit (CnA) in all three cell types, cell lysate was probed against corresponding primary antibodies by immunoblotting. Western blot analyses show the expression of CFTR, AnxA2, CnA and S100A10 in THP-1-derived monocytes and primary human monocytes. In conclusion, CFTR, S100A10, CnA and AnxA2 are expressed in THP-1-derived monocytes and primary human monocytes and regulate Cl⁻ secretion. Also, they may play a role in the pro-inflammatory molecules release. The ongoing work will confirm interaction between these proteins in the cell lines.

Keywords: annexin A2, calcineurin, CFTR, chloride, monocytes, pro-inflammatory molecules, S100A10

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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: Maria L. G. Lourenco, Viviane Y. Hibaru, Keylla H. N. P. Pereira, Fabiana F. Souza, Joao C. P. Ferreira, Simone B. Chiacchio, Luiz H. A. Machado

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Neonatal conjunctivitis, or ophthalmia, is an infection of the conjunctiva or cornea before opening the eyelids. It is believed that immunodeficiency contributes to the development of the condition. This study aims at reporting a case of ophthalmia neonatorum in a dog, in addition to its diagnosis and treatment. A litter of five pug neonates was admitted to the Sao Paulo State University (UNESP) Veterinary Hospital, Botucatu, Sao Paulo, Brazil, with complaints of ocular secretion. The neonates were five days old. The clinical examination revealed that three newborns presented swelling in the ocular region and a purulent secretion in the medial corner of the eye that was exerting pressure on the ocular globes, which are compatible with the description of this disease. The diagnosis was made based on the clinical signs and bacterial culture of the secretion, which revealed the presence of bacteria belonging to the genus Staphylococcus sp. The laboratory assays did not reveal any alterations. The treatment was instituted gently, opening the eyelids early and cleaning the purulent ocular secretion with saline solution. An ophthalmic ointment with retinol, amino acids, methionine, and chloramphenicol (Epitezan®) was prescribed four times a day for seven days. Blood plasma (2 mL/100 g) was administered subcutaneously because bacterial infections in neonates may represent a failure in the transference of passive immunity. A more thorough cleaning of the environment was also recommended. Neonatal conjunctivitis has a simple diagnosis and treatment. If not treated early, it can evolve to adherence of the eyelids to the cornea, ulceration, and perforation of the cornea. Therefore, the prognosis is favorable as long as the condition is diagnosed early, and the treatment is instituted quickly.

Keywords: ophthalmia neonatorum, neonatal infection, puppy, newborn

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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: M. A. Sohaly, M. A. Elfouly

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Parkinson's disease (PD) is a heterogeneous movement disorder that often appears in the elderly. PD is induced by a loss of dopamine secretion. Some drugs increase the secretion of dopamine. In this paper, we will simply study the stability of PD models as a nonlinear delay differential equation. After a period of taking drugs, these act as positive feedback and increase the tremors of patients, and then, the differential equation has positive coefficients and the system is unstable under these conditions. We will present a set of suggested modifications to make the system more compatible with the biodynamic system. When giving a set of numerical examples, this research paper is concerned with the mathematical analysis, and no clinical data have been used.

Keywords: Parkinson's disease, stability, simulation, two delay differential equation

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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: Petnamnueng Dettipponpong, Shuen E. Chen

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Heat stress is known to have negative effects on reproductive functions, such as follicular development and ovulation. This study aimed to investigate the specific effects of heat stress on steroid hormone secretion of ovarian follicle cells, particularly in relation to the expression of Apolipoprotein B (ApoB) and microsomal triglyceride transfer protein (MTP). The aim of the study was to understand the impact of heat stress on steroid hormone secretion in ovarian follicle cells and to explore the role of ApoB and MTP in this process. Primary granulosa and theca cells were collected from follicles and cultured under heat stress conditions (42 °C) for various time periods. Controls were maintained under normal conditions (37.5 °C ). The culture medium was collected at different time points to measure levels of progesterone and estradiol using ELISA kits. ApoB and MTP expression levels were analyzed using homemade antibodies and western blot. Data were assessed by a one-way ANOVA comparison test with Duncan’s new multiple-range test. Results were expressed as mean±S.E. Difference was considered significant at P<0.05. The results showed that heat stress significantly increased progesterone secretion in granulosa cells, with the peak observed after 13 hours of recovery under thermoneutral conditions. Estradiol secretion by theca cells was not affected. Heat stress also had a significant negative effect on granulosa cell viability. Additionally, the expression of ApoB and MTP was found to be differentially regulated by heat stress. ApoB expression in theca cells was transiently promoted, while ApoB expression in granulosa cells was consistently suppressed. MTP expression increased after 5 hours of recovery in both cell types. These findings suggest a mechanism by which chicken follicle cells export cellular lipids as very low-density lipoprotein (VLDL) in response to thermal stress. These contribute to our understanding of the role of ApoB and MTP steroidogenesis and lipid metabolism under heat stress conditions. The study involved the collection of primary granulosa and theca cells, culture under different temperature conditions, and analysis of the culture medium for hormone levels using ELISA kits. ApoB and MTP expression levels were assessed using homemade antibodies and western blot. This study aimed to address the effects of heat stress on steroid hormone secretion in ovarian follicle cells, as well as the role of ApoB and MTP in this process. The study demonstrates that heat stress stimulates steroidogenesis in granulosa cells, affecting progesterone secretion. ApoB and MTP expression were found to be differentially regulated by heat stress, indicating a potential mechanism for the export of cellular lipids in response to thermal stress.

Keywords: heat stress, granulosa cells, theca cells, steroidogenesis, chicken, apolipoprotein B, microsomal triglyceride transfer protein

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Authors: Kalsoom Rani

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Tobacco contains nicotine, which causes addiction to many toxic chemicals. In the world, people consume it in the form of smoke, chew, and sniffing, smoke of it is composed of almost 7000 active chemicals, which are very harmful to human health as well as for eye health, inhalation of tobacco smoke and fumes can accelerate and cause many blinding eye diseases. Dry eye and smoking have not been covered extensively in researches; more studies are required to unveil the relationship between smoking and dry eye. This study was conducted to determine the quantity and quality of tears in smokers. 60 subjects participated in the study, which was divided into two groups on the basis of consumption of cigarettes per day with age matched non smokers of 15-50 years. All participants have gone through a study based questioner, eye examination, and diagnostic 'Dry Eye Tests' for evaporative tears evaluation and measurement of basal tear secretion. Subjects were included in the criteria of 10 cigarettes per day with a minimum duration of 1 year; passive smokers for control groups were excluded. The study was carried out in a Medina Teaching Hospital, Faisalabad, Pakistan, ophthalmology department for the duration of 8 months. Mean values for tear break up time (TBUT), was reported 10sec with SD of +3.74 in controlled group, 5sec with SD + 2.32 in smokers and 4sec SD +3.77 heavy smokers in right eye (RE) and left eye (LE) 10.35sec with SD of +3.88 in controlled 5sec with SD + 2.3 in smokers and much reduced TBUT in heavy smokers was 3.85sec SD+2.20. Smoking has a very strong association with TRUT with a significance of P=.00 both eyes. Mean Schirmer-I value of the subjects was reported 12.6mm with SD + 8.37 in RE and 12.59mm with SD + 8.96 LE. The mean Schirmer-II test value was reported in the right, and left eye with a mean value for control was 20.23mm with SD + 8.93, 20.75mm with SD + 8.84 respectively, and in Smokers 9.90mm with SD + 5.74, and 10.07mm with SD + 6.98, and in heavy smokers 7.7mm, SD + 3.22 and 6.9, SD + 3.50 mm, association with smoking showed p=.001 in RE and .003 in LE. Smoking has deteriorated effect on both evaporative tear and aqueous tear secretion and causing symptoms of dry eye burning, itching, redness, and watering with epithelial cell damage.

Keywords: tear break-up time, basal tear secretion, smokers, dry eye

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Authors: N. A. P. Camaforte, P. M. P. Vareda, L. L. Saldanha, A. L. Dokkedal, J. M. Rezende-Neto, M. R. Senger, F. P. Silva-Jr, J. R. Bosqueiro

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Diabetes mellitus is a disease characterized by deficiency of insulin secretion and/or action which results in hyperglycemia. Nowadays, acarbose is a medicine used by diabetic people to inhibit alpha-glucosidases leading to the decreasing of post-feeding glycaemia, but with low effectiveness and many side effects. Medicinal plants have been used for the treatment of many diseases including diabetes and their action occurs through the modulation of insulin-depending processes, pancreas regeneration or inhibiting glucose absorption by the intestine. Previous studies in our laboratory showed that the treatment using two crude extracts of plants from Brazilian cerrado was able to decrease fasting blood glucose and improve glucose tolerance in streptozotocin-diabetic mice. Because of this and the importance of the search for new alternatives to decrease the hyperglycemia, we decided to evaluate the inhibitory action of two plants from Brazilian cerrado - B.H. and Myrcia bella. The enzymatic assay was performed in 50 µL of final volume using pancreatic α-amylase and maltase together with theirs commercial substrates. The inhibition potency (IC50) was determined by the incubation of eight different concentrations of both extracts and the enzymes for 5 minutes at 37ºC. After, the substrate was added to start the reaction. Glucosidases assay was evaluated measuring the quantity of p-nitrophenol in 405 nmin 384 wells automatic reader. The in vitro assay with the extracts of B.H. and M. bella showed an IC50 of 28,04µg/mL and 16,93 µg/mL for α-amilase, and 43,01µg/mL and 17 µg/mL for maltase, respectively. M. bella extract showed a higher inhibitory activity for those enzymes than B.H. extract. The crude extracts tested showed a higher inhibition rate to α-amylase, but were less effective against maltase in comparison to acarbose (IC50 36µg/mL and 9 µg/mL, respectively). In conclusion, the crude extract of B.H. and M. bella showed a potent inhibitory effect against α-amylase and showed promising results to the possible development of new medicines to treat diabetes with less or even without side effects.

Keywords: alfa-glucosidases, diabetes mellitus, glycaemia, medicinal plants

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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: Manal M. Shehata, Kawther M. Abdel-Hamid, Nashwa A. Mohamed, Marwa H. Bakr, Maged S. Mahmoud, Hala M. Elbadre

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Introduction: The worldwide rapid increase in diabetes poses a significant challenge to current therapeutic approaches. Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder β-cell regeneration. Curcumin, is a dietary spice with antioxidant activity. Aim of work: The present study was undertaken to investigate the therapeutic potential of curcumin, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Material and Methods: Fifty adult male healthy albino rats were included in the present study.They were divided into two groups: Group І: (control group) included 10 rats. Group П: (diabetic group): included 40 rats. Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ). Group II will be further subdivided into four groups (10 rats for each): Group II-a (diabetic control). Group II-b: rats were received single intraperitoneal injection of bone marrow suspension (un-fractionated bone marrow cells) prepared from rats of the same family. Group II-c: rats were treated with curcumin orally by gastric intubation for 6 weeks. Group II-d: rats were received a combination of single bone marrow transplantation and curcumin for 6 weeks. After 6 weeks, blood glucose, insulin levels were measured and the pancreas from all rats were processed for Histological, Immunohistochemical and morphometric examination. Results: Diabetic group, showed progressive histological changes in the pancreatic islets. Treatment with either curcumin or bone marrow transplantation improved the structure of the islets and reversed streptozotocin-induced hyperglycemia and hypoinsulinemia. Combination of curcumin and bone marrow transplantation elicited more profound alleviation of streptozotocin-induced changes including islet regeneration and insulin secretion. Conclusion: The use of natural antioxidants combined with bone marrow transplantation to induce pancreatic regeneration is a promising strategy in the management of diabetes.

Keywords: diabtes, panceatic islets, bone marrow transplantation, curcumin

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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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Authors: Goodarzvand Fatemeh, Soori Rahman, Effatpanah Mohammad, Ajbarnejad Ali

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Attention deficit hyperactivity disorder (ADHD) is characterized by a pervasive pattern of developmentally inappropriate inattentive, impulsive and hyperactive behaviors that typically begin during the preschool ages and often persist into adulthood. This disorder is related to autism and schizophrenia and other psychological disorders and clinical conditions such as insulin resistance and they may operate through common pathways, and treatments used exclusively for one of these conditions may prove beneficial for the others. While ADHD is not fully understood as developmental disorder with an etiopathogeny, but studies show that core symptom of disorder was associated with and increased by the interleukins IL-13, where relation of IL-13 with inattention was notable. Regular exercise improves functions associated with attention deficit hyperactivity disorder (ADHD). However, the impact of exercise on cytokines associated with the disease activity remains relatively unexplored. The aim of this study was to examine the effects of 6 weeks high intensity by intervals training (HIIT) on IL-13 levels and insulin resistance in boys with ADHD. Twenty eight boys with ADHD disease in a range of 12-18 year of old participated in this study as the subject. Subjects were divided into control group (n=10) and training group (n=18) randomly. The training group performed progressive HIIT program, 3 days a week for 6 weeks. The control group was in absolute rest at the same time. The results showed that after six weeks of HIIT, IL-13 decreased in the exercise group and these changes achieved (p= 0.002) statistical significance (p < 0.005). The results suggest HIIT with specific intensity and duration utilized in this study had not significant effect on insulin resistance levels in female patients with ADHD (p=0.39), while the difference in the average control and case group was decreased.

Keywords: attention deficit hyperactivity disorder, interleukin 13, insulin resistance, high intensity by intervals training

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Authors: Izzatul Ulfana, Angga Pratomo Cahyadi, Rimayanti, Widjiati

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Freezing oocyte could cause temperature stress. Temperature stress triggers cell damage. Insulin Transferrin Selenium (ITS) and Heat Shock Protein 70 (HSP70) had been used to prevent damage to the oocyte after freezing. ITS and HSP70 could cause the difference protective effect. The aim of this research was to obtain an effective cryoprotectant for freezing local goat oocyte in cumulus cells change. The research began by collecting the ovary from a local slaughterhouse in Indonesia, aspiration follicle, in vitro maturation and the freezing had been used vitrification method. Examination of the morphology cells by native staining method. Data on the calculation morphology oocyte analyzed by Kruskall-Wallis Test. After the Kruskall-Wallis Test which indicated significance, followed by Mann-Whitney Test to compare between treatment groups. As a result, cryoprotectant ITS has the best culumus cells after warming

Keywords: Insulin Transferrin Selenium, Heat Shock Protein 70, cryoprotectant, vitrification

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Authors: Gulnaz Khan, Meha F. Aftab, Munazza Murtaza, Rizwana S. Waraich

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Advanced glycation end products (AGEs) precursor and its abnormal accumulation cause damage to various tissues and organs. AGEs have pathogenic implication in several diseases including diabetes. Existing AGEs inhibitors are not in clinical use, and there is a need for development of novel inhibitors. The present investigation aimed at identifying the novel AGEs inhibitors and assessing their mechanism of action for treating insulin resistance in mice model of diabetes. Novel derivatives of benzylidene of indan-1,3-dione were synthesized. The compounds were selected to study their action mechanism in improving insulin resistance, in vitro, in human hepatocytes and murine adipocytes and then, in vivo, in mice genetic model of diabetes (db/db). Mice were treated with novel derivatives of benzylidene of indane 1,3-dione. AGEs mediated ROS production was measured by dihydroethidium fluorescence assay. AGEs level in the serum of treated mice was observed by ELISA. Gene expression of receptor for AGEs (RAGE), PPAR-gamma, TNF-alpha and GLUT-4 was evaluated by RT-PCR. Glucose uptake was measured by fluorescent method. Microscopy was used to analyze glycogen synthesis in muscle. Among several derivatives of benzylidene of indan-1,3-dione, IDD-24, demonstrated highest inhibition of AGESs. IDD-24 significantly reduced AGEs formation and expression of receptor for advanced glycation end products (RAGE) in fat, liver of db/db mice. Suppression of AGEs mediated ROS production was also observed in hepatocytes and fat cell, after treatment with IDD-24. Glycogen synthesis was increased in muscle tissue of mice treated with IDD-24. In adipocytes, IDD-24 prevented AGEs induced reduced glucose uptake. Mice treated with IDD-24 exhibited increased glucose tolerance, serum adiponectin levels and decreased insulin resistance. The result of present study suggested that IDD-24 can be a possible treatment target to address glycotoxins induced insulin resistance.

Keywords: advance glycation end product, hyperglycemia, indan-1, 3-dione, insulin resistance

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Authors: Natalia Moreno-Castellanos, Amaia Rodriguez, Gema Frühbeck

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Introduction: In adipocytes, the cytoskeleton undergoes important expression and distribution in adipocytes rearrangements during adipogenesis and in obesity. Indeed, a role for these proteins in the regulation of adipocyte differentiation and response to insulin has been demonstrated. Recently, septins have been considered as new components of the cytoskeletal network that interact with other cytoskeletal elements (actin and tubulin) profoundly modifying their dynamics. However, these proteins have not been characterized as yet in adipose tissue. In this work, were examined the cellular, molecular and functional features of a member of this family, septin 11 (SEPT11), in adipocytes and evaluated the impact of obesity on the expression of this protein in human adipose tissue. Methods: Adipose gene and protein expression levels of SEPT11 were analysed in human samples. SEPT11 distribution was evaluated by immunocytochemistry, electronic microscopy, and subcellular fractionation techniques. GST-pull down, immunoprecipitation and a Yeast-Two Hybrid (Y2H) screening were used to identify the SEPT11 interactome. Gene silencing was employed to assess the role of SEPT11 in the regulation of insulin signaling and lipid metabolism in adipocytes. Results: SEPT11 is expressed in human adipocytes, and its levels increased in both omental and subcutaneous adipose tissue in obesity, with SEPT11 mRNA content positively correlating with parameters of insulin resistance in subcutaneous fat. In non-stimulated adipocytes, SEPT11 immunoreactivity showed a ring-like distribution at the cell surface and associated to caveolae. Biochemical analyses showed that SEPT11 interacted with the main component of caveolae, caveolin-1 (CAV1) as well as with the fatty acid-binding protein, FABP5. Notably, the three proteins redistributed and co-localized at the surface of lipid droplets upon exposure of adipocytes to oleate. In this line, SEPT11 silencing in 3T3-L1 adipocytes impaired insulin signaling and decreased insulin-induced lipogenesis. Conclusions: Those findings demonstrate that SEPT11 is a novel component of the adipocyte cytoskeleton that plays an important role in the regulation of lipid traffic, metabolism and can thus represent a potential biomarker of insulin resistance in obesity in adipocytes through its interaction with both CAV1 and FABP5.

Keywords: caveolae, lipid metabolism, obesity, septins

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Authors: Cristian Baldini

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‘Diabesity’ is a term for diabetes occurring in the context of obesity. The positive effect of LCHF diets (low-carb, high-fat diets) is well documented: LCHF diets are at least as effective as other dietary strategies for reducing body weight, improving glycaemic control, and reducing both hyperinsulinaemia and blood glucose (reduction of HbA1c) in type 2 diabetes and have unique positive effects on blood lipid concentrations and cardiovascular risk factors. Also, in obese insulin-resistant women, food fried in extra-virgin olive oil significantly reduced both insulin and C-peptide responses after a meal. This case study shows that if combined, both dietary strategies produce a strong effect on blood glucose, resulting in a “forced” reduction of exogenous insulin injection to avoid the problem of hypoglycaemia. Blood tests after three months of this dietary treatment show how HbA1c, triglycerides, and blood lipid profile (LDL, HDL, Total Cholesterol) are improved despite the reduction of exogenous insulin injection of 80% with a parallel body weight decrease of 15%. For continuous glucose monitoring (CGM), the patient used FreeStyle Libre before and after the dietary treatment. In order to check general body functions and glycosuria, the patient used the urine test Multistix 10 SG Siemens.

Keywords: diabetes, obesity, diabesity, fat, fried foods

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Authors: Caio E. G. Reis, Sara Wassell, Adriana L. Porto, Angélica A. Amato, Leslie J. C. Bluck, Teresa H. M. da Costa

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Background: Multiple epidemiologic studies have consistently reported association between increased coffee consumption and a lowered risk of Type 2 Diabetes Mellitus. However, the mechanisms behind this finding have not been fully elucidated. Objective: We investigate the effect of coffee (caffeinated and decaffeinated) on glucose effectiveness and insulin sensitivity using the stable isotope minimal model protocol with oral glucose administration in healthy men. Design: Fifteen healthy men underwent 5 arms randomized crossover single-blinding (researchers) clinical trial. They consumed decaffeinated coffee, caffeinated coffee (with and without sugar), and controls – water (with and without sugar) followed 1 hour by an oral glucose tolerance test (75 g of available carbohydrate) with intravenous labeled dosing interpreted by the two compartment minimal model (225 minutes). One-way ANOVA with Bonferroni adjustment were used to compare the effects of the tested beverages on glucose metabolism parameters. Results: Decaffeinated coffee resulted in 29% and 85% higher insulin sensitivity compared with caffeinated coffee and water, respectively, and the caffeinated coffee showed 15% and 60% higher glucose effectiveness compared with decaffeinated coffee and water, respectively. However, these differences were not significant (p > 0.10). In overall analyze (0 – 225 min) there were no significant differences on glucose effectiveness, insulin sensitivity, and glucose and insulin area under the curve between the groups. The beneficial effects of coffee did not seem to act in the short-term (hours) on glucose metabolism parameters mainly on insulin sensitivity indices. The benefits of coffee consumption occur in the long-term (years) as has been shown in the reduction of Type 2 Diabetes Mellitus risk in epidemiological studies. The clinical relevance of the present findings is that there is no need to avoid coffee as the drink choice for healthy people. Conclusions: The findings of this study demonstrate that the consumption of caffeinated and decaffeinated coffee with or without sugar has no acute effects on glucose metabolism in healthy men. Further researches, including long-term interventional studies, are needed to fully elucidate the mechanisms behind the coffee effects on reduced risk for Type 2 Diabetes Mellitus.

Keywords: coffee, diabetes mellitus type 2, glucose, insulin

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Authors: Hoda M. Eid, Abir Nachar, Farah Thong, Gary Sweeney, Pierre S. Haddad

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Caffeic acid methyl ester (CAME) and caffeic ethyl esters (CAEE) were previously reported to potently stimulate glucose uptake in cultured C2C12 skeletal muscle cells via insulin-independent mechanisms involving the activation of adenosine monophosphate-activated protein kinase (AMPK). In the present study, we investigated the effect of the two compounds on the translocation of glucose transporter GLUT4 in L6 skeletal muscle cells. The cells were treated with the optimum non-toxic concentration (50 µM) of either CAME or CAEE for 18 h. Levels of GLUT4myc at the cell surface were measured by O-phenylenediamine dihydrochloride (OPD) assay. The effects of CAME and CAEE on GLUT1 and GLUT4 protein content were also measured by western immunoblot. Our results show that CAME and CAEE significantly increased glucose uptake, GLUT4 translocation and GLUT4 protein content. Furthermore, the effect of the two CA esters on two insulin-sensitive cell lines: H4IIE rat hepatoma and 3T3-L1 adipocytes were investigated. CAME and CAEE reduced the enzymatic activity of the key hepatic gluconeogenic enzyme glucose-6-phosphatase in a concentration-dependent manner. In addition, they exerted a concentration-dependent antiadipogenic effect on 3T3-L1 cells. Mitotic clonal expansion (MCE), a prerequisite for adipocytes differentiation was also concentration-dependently inhibited. The two compounds abrogated lipid droplet accumulation, blocked MCE and maintained cells in fibroblast-like state when applied at the maximum non-toxic concentration (100 µM). In addition, the expression of the early key adipogenic transcription factors CCAAT enhancer-binding protein beta (C/EBP-β) and the master regulator of adipogenesis peroxisome-proliferator-activated receptor gamma (PPAR-γ) were inhibited. We, therefore, conclude that CAME and CAEE exert pleiotropic benefits in several insulin-sensitive cell lines through insulin-independent mechanisms involving AMPK, hence they may treat obesity, diabetes and other metabolic diseases.

Keywords: type 2 diabetes mellitus, insulin resistance, GLUT4, Akt, AMPK.

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Authors: Daniel Zarzo Montes, Manuel Zarzo Castelló

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Proteins play a fundamental role in biology, but their structure is complex, and it is a challenge for teachers to conceptually explain the differences between their primary, secondary, tertiary, and quaternary structures. On the other hand, there are currently many computer programs to visualize the 3D structure of proteins, but they require advanced training and knowledge. Moreover, it becomes difficult to visualize the sequence of amino acids in these models, and how the protein conformation is reached. Given this drawback, a simple and instructive procedure is proposed in order to teach the protein structure to undergraduate and graduate students. For this purpose, insulin has been chosen because it is a protein that consists of 51 amino acids, a relatively small number. The methodology has consisted of the use of plastic atom models, which are frequently used in organic chemistry and biochemistry to explain the chirality of biomolecules. For didactic purposes, when the aim is to teach the biochemical foundations of proteins, a manipulative system seems convenient, starting from the chemical structure of amino acids. It has the advantage that the bonds between amino acids can be conveniently rotated, following the pattern marked by the 3D models. First, the 51 amino acids were modeled, and then they were linked according to the sequence of this protein. Next, the three disulfide bonds that characterize the stability of insulin have been established, and then the alpha-helix structure has been formed. In order to reach the tertiary 3D conformation of this protein, different interactive models available on the Internet have been visualized. In conclusion, the proposed methodology seems very suitable for biology and biochemistry students because they can learn the fundamentals of protein modeling by means of a manipulative procedure as a basis for understanding the functionality of proteins. This methodology would be conveniently useful for a biology or biochemistry laboratory practice, either at the pre-graduate or university level.

Keywords: protein structure, 3D model, insulin, biomolecule

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Authors: Muluneh Ademe, Zeleke Mekonnen

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Objective: to determine the level of bacterial contamination of reused insulin syringes among diabetic patients. Method: A facility based cross-sectional study was conducted among diabetic patients. Data on socio-demographic variables, history of injection syringe reuse, and frequency of reuse of syringes were collected using predesigned questionnaire. Finally, the samples from the syringes were cultured according to standard microbiological techniques. Result: Eighteen diabetic patients at Jimma University Hospital participated. A total of 83.3% of participants reused a single injection syringe for >30 consecutive injections, while 16.7% reused for >30 injections. Our results showed 22.2% of syringes were contaminated with methicillin-resistant Staphylococcus aures. Conclusion: We conclude reuse of syringe is associated with microbial contamination. The findings that 4/18 syringes being contaminated with bacteria is an alarming situation. A mechanism should be designed for patients to get injection syringes with affordable price. If reusing is not avoidable, reducing number of injections per a single syringe and avoiding needle touching with hand or other non-sterile material may be an alternative to reduce the risk of contamination.

Keywords: diabetes mellitus, Ethiopia, subcutaneous insulin injection, syringe reuse

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Authors: Hui-Qin Xu, Xing Lv, Yu-Han Tao

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The depth study aimed on the mechanism of morroniside in protecting diabetic nephropathy. The diabetic mice models with blood glucose above 15mmol/L were divided into model, aminoguanidine, metformin, captopril, morroniside low-dose, and morroniside high-dose groups. And normal group was set simultaneously. All groups were fed with high AGEs food except normal group. Each group was intragastric administration of the corresponding medicine except model and normal groups. After 12 weeks, all the indictors were measured. It showed that the morroniside could reduce blood glucose significantly, urinary protein, serum urea nitrogen, creatine, pathological changes, AGEs levels, renal cortex RAGE mRNA and RAGE protein expression levels; increase food consumption, water intake, urine volume, insulin secretion. As a conclusion, morroniside from cornus officinalis can protect renal in diabetic mice, its mechanism may be related to the proliferation of islet cells, rectify glycometabolism, reduce serum and kidney AGEs content, and descend renal RAGEmRNA and RAGE protein expression levels.

Keywords: cornus officinalis, diabetic nephropathy, morroniside, RAGE protein

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