Search results for: Diabetes mellitus

Authors: Dalia O. Saleha, Gehad A. Abdel Jaleela, Sally W. Al-Awdana

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Diabetes mellitus (DM) is known to exacerbate cerebral ischemic injury. The present study aimed to investigate the anti-oxidant and anti-inflammatory effects of oral supplementation of melatonin (MLN) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in streptozotocin (STZ)-induced hyperglycemic rats. Hyperglycemia was induced by a single injection of STZ (55mg/kg; i.p.), six weeks later the cerebral injury was induced by MCAO/Re. Twenty-four hours after the MCAO/Re the MLN (10 mg/kg) was injected for 14 consecutive days. Results of the present study revealed that MCAO/Re in STZ-induced hyperglycemia in rats causes an increase in the oxidative stress biomarkers; it increased brain lipid peroxidation (measured as malondialdehyde; MDA) and brain level of nitric oxide (NO). Moreover, MCAO/Reproduces a prominent increase in the brain inflammatory markers viz. interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis nuclear factor-alpha (TNF-α). Oral treatment of MCAO/Re in STZ-induced hyperglycemic rats with MLN (10 mg/kg) for two weeks restored the brain levels of MDA, GSH, NO, IL-6, IL-1β and the TNF-α. MLN succeeded to suppress the exacerbation of damage in the brain of hyperglycemic rats. These results suggest that daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-oxidant and anti-inflammatory effects in the brain.

Keywords: melatonin, brain injury, cerebral ischemia/reperfusion, hyperglycemia, rats

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Authors: Agnieszka H. Ludwig-Slomczynska, Michal T. Seweryn, Przemyslaw Kapusta, Ewelina Pitera, Katarzyna Cyganek, Urszula Mantaj, Lucja Dobrucka, Ewa Wender-Ozegowska, Maciej T. Malecki, Pawel Wolkow

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Obesity results from an imbalance between energy intake and its expenditure. Genome-Wide Association Study (GWAS) analyses have led to discovery of only about 100 variants influencing body mass index (BMI), which explain only a small portion of genetic variability. Analysis of gene epistasis gives a chance to discover another part. Since it was shown that interaction and communication between nuclear and mitochondrial genome are indispensable for normal cell function, we have looked for epistatic interactions between the two genomes to find their correlation with BMI. Methods: The analysis was performed on 366 T1DM patients using Illumina Infinium OmniExpressExome-8 chip and followed by imputation on Michigan Imputation Server. Only genes which influence mitochondrial functioning (listed in Human MitoCarta 2.0) were included in the analysis – variants of nuclear origin (MAF > 5%) in 1140 genes and 42 mitochondrial variants (MAF > 1%). Gene expression analysis was performed on GTex data. Association analysis between genetic variants and BMI was performed with the use of Linear Mixed Models as implemented in the package 'GENESIS' in R. Analysis of association between mRNA expression and BMI was performed with the use of linear models and standard significance tests in R. Results: Among variants involved in epistasis between mitochondria and nucleus we have identified one in mitochondrial transcription factor, TFB2M (rs6701836). It interacted with mitochondrial variants localized to MT-RNR1 (p=0.0004, MAF=15%), MT-ND2 (p=0.07, MAF=5%) and MT-ND4 (p=0.01, MAF=1.1%). Analysis of the interaction between nuclear variant rs6701836 (nuc) and rs3021088 localized to MT-ND2 mitochondrial gene (mito) has shown that the combination of the two led to BMI decrease (p=0.024). Each of the variants on its own does not correlate with higher BMI [p(nuc)=0.856, p(mito)=0.116)]. Although rs6701836 is intronic, it influences gene expression in the thyroid (p=0.000037). rs3021088 is a missense variant that leads to alanine to threonine substitution in the MT-ND2 gene which belongs to complex I of the electron transport chain. The analysis of the influence of genetic variants on gene expression has confirmed the trend explained above – the interaction of the two genes leads to BMI decrease (p=0.0308). Each of the mRNAs on its own is associated with higher BMI (p(mito)=0.0244 and p(nuc)=0.0269). Conclusıons: Our results show that nuclear-mitochondrial epistasis can influence BMI in T1DM patients. The correlation between transcription factor expression and mitochondrial genetic variants will be subject to further analysis.

Keywords: body mass index, epistasis, mitochondria, type 1 diabetes

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Authors: Md. Alauddin, Md. Ruhul Amin, Md. Omar Faruque, Muhammad Ali Siddiquee, Zakir Hossain Howlader, Mohammad Asaduzzaman

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Diabetes and hypertension are the major lifestyle related diseases. The α-amylase and angiotensin converting enzymes (ACE) are the key enzymes that regulate diabetes and hypertension. The aim was to develop a drug for the treatment of diabetes and hypertension. The Rice Bran (RB) sample (Oryza sativa; BRRI-Dhan-84) was collected from the Bangladesh Rice Research Institute (BRRI), and rice bran proteins were isolated and hydrolyzed by hydrolyzing enzyme alcalase and trypsin. In vivo experiment suggested that rice bran bioactives has an effect on regulating the expression of several key gluconeogenesis and lipogenesis-regulating genes, such as glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, and fatty acid synthase. The above genes have a connection of regulating the glucose level, lipids profile as well as act as an anti-inflammatory agent. A molecular docking, bioinformatics and in vitro experiments were performed. We found rice bran protein hydrolysates significantly (<0.05) influence the peptide concentration in the case of trypsin, alcalase, and (trypsin + alcalase) digestion. The in vitro analysis found that protein hydrolysate significantly (<0.05) reduced diabetic and hypertension as well as oxidative stress. A molecular docking study showed that the YY and IP peptide have a significantly strong binding affinity to the active site of the ACE enzyme and α-amylase with -7.8Kcal/mol and -6.2Kcal/mol, respectively. The Molecular dynamics (MD) simulation and Swiss ADME data analysis showed that less toxicity risk, good physicochemical properties, pharmacokinetics, and drug-likeness with drug scores 0.45 and 0.55 of YY and IP peptides, respectively. Thus, rice bran bioactive could be a good candidate for the treatment of diabetes and hypertension.

Keywords: anti-hypertensive and anti-hyperglycemic, anti-oxidative, bioinformatics, in vitro study, rice bran proteins and peptides

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Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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Authors: Raad Nari, Maura Moriaty, Maha T. Barakat

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Introduction: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs with a unique mechanism of action. They are used to improve glycaemic control in adults with type 2 diabetes by enhancing urinary glucose excretion. In the UAE, there has been certainly an increased use of these medications. As with any new medication, there are safety considerations related to their use in patients with type two diabetes. A retrospective study was conducted at the three main centres of the Imperial College London Diabetes Centre. Methodology: All patients in electronic database (Diamond) from October 2014 to October 2017 were included with a minimum of six months usage of sodium glucose co-transporter inhibitors that comprise canagliflozin, dapagliflozin and empagliflozin. There were 15 paired sample biochemical and clinical correlations. The analysis was done at the start of the study, three months and six months apart. SPSS version 24 was used for this study. Conclusion: This study of sodium glucose co-transporter-2 inhibitors used showed significant reductions in weight, glycated haemoglobin A1C, systolic and diastolic blood pressures. As the case with systematic reviews, there were similar changes in liver enzymes, raised total cholesterol, low density lipopoptein and high density lipoprotein. There was slight improvement in estimated glomerular filtration rate too. Our analysis also showed that they increased in the incidence of urinary tract symptoms and incidence of urinary tract infections.

Keywords: SGLT2 inhibitors dapagliflozin empagliflozin canagliflozin, adverse effects, amputation diabetic ketoacidosis DKA, urinary tract infection

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Authors: M. Wisnu Pamungkas, Patrianef Darwis

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Introduction: Critical limb ischemia (CLI) is a vascular disease that has a significant amputation and mortality risk with diabetes mellitus, the most significant risk factor in CLI, is very common among Indonesian. Endovascular intervention (EVI) is preferred in treating CLI because it is noninvasive and effective. Balloon angioplasty and stent angioplasty are the most common method of EVI in Indonesia. This study aims to compare the effectiveness of balloon angioplasty and stent angioplasty on wound healing in CLI. Method: A cross-sectional study enrolled 90 subjects of CLI who underwent endovascular intervention using balloon angioplasty and stent angioplasty from January 2013 to July 2017 in dr. Cipto Mangunkusumo General Hospital, Jakarta. The wound healing period between balloon angioplasty dan stent angioplasty was analyzed using unpaired T-test with p<0,05 considered as statistically significant. Data of intervention method wound healing period, and subjects characteristic data (age, amputation, BMI, smoking habit, DM, occlusion site, and blood profile) were obtained. Result: The wound healing period in balloon angioplasty and stent angioplasty distributed normally. Mean value of wound healing period in balloon angioplasty and stent angioplasty are 84,8+/-2,423 and 59,93 +/- 2,423 days with a mean difference of 25 days. The difference in wound healing period in both groups is statically significant (p<0,05). The amputation event in balloon angioplasty and stent angioplasty is 22 and 16 event with no difference statistically. Conclusion: Stent angioplasty is a better method than balloon angioplasty for wound healing in patients with CLI.

Keywords: critical limb ischemia, endovascular intervention, wound healing, angioplasty

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Authors: Soumaya Mrabet, Taieb Ach, Imen Akkari, Amira Atig, Neirouz Ghannouchi, Koussay Ach, Elhem Ben Jazia

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Introduction: Celiac disease (CD) is an immune-mediated small intestinal disorder that occurs in genetically susceptible people. It is significantly associated with other autoimmune disorders represented mainly by type 1 diabetes and autoimmune dysthyroidism. The aim of our study is to determine the prevalence and the type of the various autoimmune diseases associated with CD in adult patients. Material and methods: This is a retrospective study including patients diagnosed with CD, explored in Internal Medicine, Gastroenterology and Endocrinology and Diabetology Departments of the Farhat Hached University Hospital, between January 2005 and January 2016. The diagnosis of CD was confirmed by serological tests and duodenal biopsy. The screening of autoimmune diseases was based on physical examination, biological and serological tests. Results: Sixty five patients with a female predominance were included, 48women (73.8%) and 17 men (26.2%). The mean age was 31.8 years (17-75). A family history of CD or other autoimmune diseases was present in 5 and 10 patients respectively. Clinical presentation of CD was made by recurrent abdominal pain in 49 cases, diarrhea in 29 cases, bloating in 17 cases, constipation in 25 cases and vomiting in 8 cases. Autoimmune diseases associated with CD were found in 30 cases (46.1%): type 1 diabetes in 15 patients attested by the positivity of anti-GAD antibodies in 11 cases and anti-IA2 in 4 cases, Hashimoto thyroiditis in 8 cases confirmed by the positivity of anti-TPO antibodies, Addison's disease in 2 patients, Anemia of Biermer in 2 patients, autoimmune hepatitis, Systemic erythematosus lupus, Gougerot Sjögren syndrome, rheumatoid arthritis, Vitiligo and antiphospholipid syndrome in one patient each. CD was associated with more than one autoimmune disease defining multiple autoimmune syndrome in 2 female patients. The first patient had Basedow disease, Addison disease and type 1 diabetes. The second patient had systemic erythematosus lupus and Gougerot Sjögren syndrome. Conclusion: In our study autoimmune diseases were associated with CD in 46.1% of cases and were dominated by diabetes and dysthroidism. After establishing the diagnosis of CD the search of associated autoimmune diseases is necessary in order to avoid any therapeutic delay which can alter the prognosis of the patient.

Keywords: association, autoimmune thyroiditis, celiac disease, diabetes

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Authors: Srijoni Banerjee

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Sequences of some of the candidate genes (e.g., CPE, CDKAL1, GCKR, HSD11B1, IGF2BP2, IRS1, LPIN1, PKLR, TNF, PPARG) implicated in some of the complex disease, e.g. Type II diabetes in man has been compared with other species to investigate phylogenetic affinity. Based on mRNA sequence of these genes of 7 to 8 species, using bioinformatics tools Mega 5, Bioedit, Clustal W, distance matrix was obtained. Phylogenetic trees were obtained by NJ and UPGMA clustering methods. The results of the phylogenetic analyses show that of the species compared: Xenopus l., Danio r., Macaca m., Homo sapiens s., Rattus n., Mus m. and Gallus g., Bos taurus, both NJ and UPGMA clustering show close affinity between clustering of Homo sapiens s. (Man) with Rattus n. (Rat), Mus m. species for the candidate genes, except in case of Lipin1 gene. The results support the functional similarity of these genes in physiological and biochemical process involving man and mouse/rat. Therefore, in understanding the complex etiology and treatment of the complex disease mouse/rate model is the best laboratory choice for experimentation.

Keywords: phylogeny, candidate gene of type-2 diabetes, CPE, CDKAL1, GCKR, HSD11B1, IGF2BP2, IRS1, LPIN1, PKLR, TNF, PPARG

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Authors: Hamzeh Awad

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Disability is considered to be a worldwide complex phenomenon which rising at a phenomenal rate and caused by many different factors. Chronic diseases such as cardiovascular disease and diabetes can lead to mobility disability in particular and disability in general. The ICF is an integrative bio-psycho-social model of functioning and disability and considered by the World Health Organization (WHO) to be a reference for disability classification using its categories and core set to classify disorder’s functional limitations. Specialist programs at Sultan Bin Abdul Aziz Humanitarian City (SBAHC) are providing both inpatient and outpatient services have started to implement the ICF and use it as a problem solving tool in Rehab. Diabetes is leading contributing factor for disability and considered epidemic in several Gulf countries including the Kingdom of Saudi Arabia (KSA), where its prevalence continues to increase dramatically. Metabolic disorders, mainly diabetes are not well covered in Rehab field. The purpose of this study is present to research and clinical rehabilitation field of DREAM and ICF as a framework in clinical and research setting in Rehab service. Also, shed the light on using the ICF as problem solving tool at SBAHC. There are synergies between disability causes and wider public health priorities in relation to both chronic disease and disability prevention. Therefore, there is a need for strong advocacy and understanding of the role of ICF as a reference in Rehab settings in Middle East if we wish to seize the opportunity to reverse current trends of acquired disability in the region.

Keywords: international classification of functioning, disability and health (ICF), prototype, rehabilitation and diabetes

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Authors: Li Jiuen Ong, Magdalin Cheong, Sri Rahayu, Lek Alexander, Pei Ting Tan

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Background: Previous programme evaluations from the diabetes training programme conducted in Changi General Hospital revealed that healthcare professionals (HCPs) are keen to receive advance diabetes training and education, specifically in medical, nutritional therapy. HCPs also expressed a preference for interactive activities over didactic teaching methods to enhance their learning. Since the War on Diabetes was initiated by MOH in 2016, HCPs are challenged to be actively involved in continuous education to be better equipped to reduce the growing burden of diabetes. Hence, streamlining training to incorporate an element of fun is of utmost importance. Aim: The nutrition programme incorporates game play using an interactive board game that aims to provide a more conducive and less stressful environment for learning. The board game could be adapted for training of community HCPs, health ambassadors or caregivers to cope with the increasing demand of diabetes care in the hospital and community setting. Methodology: Stages for game’s conception (Jaffe, 2001) were adopted in the development of the interactive board game ‘Sweet Score™ ’ Nutrition concepts and topics in diabetes self-management are embedded into the game elements of varying levels of difficulty (‘Easy,’ ‘Medium,’ ‘Hard’) including activities such as a) Drawing/ sculpting (Pictionary-like) b)Facts/ Knowledge (MCQs/ True or False) Word definition) c) Performing/ Charades To study the effects of game play on knowledge acquisition and perceived experiences, participants were randomised into two groups, i.e., lecture group (control) and game group (intervention), to test the difference. Results: Participants in both groups (control group, n= 14; intervention group, n= 13) attempted a pre and post workshop quiz to assess the effectiveness of knowledge acquisition. The scores were analysed using paired T-test. There was an improvement of quiz scores after attending the game play (mean difference: 4.3, SD: 2.0, P<0.001) and the lecture (mean difference: 3.4, SD: 2.1, P<0.001). However, there was no significance difference in the improvement of quiz scores between gameplay and lecture (mean difference: 0.9, 95%CI: -0.8 to 2.5, P=0.280). This suggests that gameplay may be as effective as a lecture in terms of knowledge transfer. All the13 HCPs who participated in the game rated 4 out of 5 on the likert scale for the favourable learning experience and relevance of learning to their job, whereas only 8 out of 14 HCPs in the lecture reported a high rating in both aspects. 16. Conclusion: There is no known board game currently designed for diabetes training for HCPs.Evaluative data from future training can provide insights and direction to improve the game format and cover other aspects of diabetes management such as self-care, exercise, medications and insulin management. Further testing of the board game to ensure learning objectives are met is important and can assist in the development of awell-designed digital game as an alternative training approach during the COVID-19 pandemic. Learning through gameplay increases opportunities for HCPs to bond, interact and learn through games in a relaxed social setting and potentially brings more joy to the workplace.

Keywords: active learning, game, diabetes, nutrition

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Authors: Maryam Nabati, Mahmood Moosazadeh, Ehsan Soroosh, Hanieh Shiraj, Mahnaneh Gholami, Ali Ghaemian

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Background: Reported effects of obesity on the extent of angiographic coronary artery disease(CAD) have beeninconsistent. The present study aimed to investigate the relationships between the indices of obesity and otheranthropometric markers with the extent of CAD. Methods: This study was conducted on 1008 consecutive patients who underwent coronary angiography. Bodymass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) wereseparately calculated for each patient. Extent, severity, and complexity of CAD were determined by the Gensini andSYNTAX scores. Results: According to the results, there was a significant inverse correlation between the SYNTAX score with BMI(r = − 0.110; P < 0.001), WC (r = − 0.074; P = 0.018), and WHtR (r = − 0.089; P = 0.005). Furthermore, a significant inversecorrelation was observed between the Gensini score with BMI (r = − 0.090; P = 0.004) and WHtR (r = − 0.065; P =0.041). However, the results of multivariate linear regression analysis did not show any association between theSYNTAX and Gensini scores with the indices of obesity and overweight. On the other hand, the patients with anunhealthy WC had a higher prevalence of diabetes mellitus (DM) (P = 0.004) and hypertension (HTN) (P < 0.001) compared to the patients with healthy values. Coexistence of HTN and DM was more prevalent in subjects with anunhealthy WC and WHR compared to that in those with healthy values (P = 0.002 and P = 0.032, respectively). Conclusion: It seems that the anthropometric indices of obesity are not the predictors of the angiographic severityof CAD. However, they are associated with an increased risk of cardiovascular risk factors and higher risk profile.

Keywords: body mass index, BMI, coronary artery disease, waist circumference

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Authors: Kerdsiri Hongthai, Darunee Jongudomkarn, Rutja Phuphaibul

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In Thailand, many adults in rural areas migrate to seek employ¬ment resulting in skipped-generation family where grandparents care for grandchildren with no other adults present. This is a preliminary study using qualitative case study methods, aimed to explore the situations of older adult grandparents' experiences in skipped-generation family in North-East of Thailand. Data were collected by in-depth inter¬views with 6 grandparents living in skipped-generation families; 5 females and 1 males grandparents, aged 62-75, some of them have diabetes mellitus, hypertension, during November to December, 2017. The finding themes are: ‘Caught up in the middle’: the older adults were pleased to have grandchildren but, at the same time, acknowledge the burden that this placed on them, especially when the migrant children failed to send enough money back to support the family. ‘Getting bad health’: they reported to be fatigued and stressed due to burden of caring for their grandchildren without support. This situation can aggravate problems of poor health status and be worsening economic status of the grandparents. In some cases of deprivation, the grandparents feel that having to be the sole care providers of their grandchildren can negative adversely affect their mental status. It is important to find out in other sectors similar to Thailand and lead to more in-depth research to answer the research questions about policy and social support in skipped-generation family in the future.

Keywords: older adult grandparents, experiences, principle care giver, skipped-generation family

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Authors: Ivory A. Rulona, Jarungchai Anton S. Vatanagul

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Background: Depression is common after stroke with quoted rates ranging from 18% to 61%. 8 Mood disturbance is common after stroke and may present as depression or anxiety. Psychological mood disturbance is associated with higher rates of mortality, long term disability, and hospital readmission. Objectives: To investigate the incidence of post-stroke depression in a tertiary hospital in Cebu City, Philippines and to determine its associated factors. The study is designed to be prospective, descriptive, cross-sectional survey. Participants: Adult patients seen and diagnosed to have stroke either infarct or hemorrhage within the period of January 1 to July 31, 2014. Results: A total of 100 patients with stroke were interviewed using the 17-item Hamilton Depression Rating Scale (HDRS) questionnaire. The average age of the respondents was 60.50 years old ±1.18, majority were males (55%), 83% were married, and 81% were employed. The most common co-morbidity was hypertension 78% followed by diabetes mellitus at 50%. Moreover, 39% of these patients had stroke in months, 26% in years, and 18% in weeks. The average functional capacity based on Modified Rankin Scale was 2.14+/-0.14. Among 100 patients, a total of 30 patients (30%) had depression: 2 (2%) very severe, 5 (5%) moderate and 23 (23%) had mild depression while 70 patients (70%) had no depression. Stroke located at the dominant hemisphere was not associated with severe depression (p=0.102). A similar trend was also noted among those with stroke at the right side (p=0.183), pons (p=0.634), bilateral (p=0.776), and midbrain (p=0.336). Conclusion: This study showed that majority of stroke patients were males with average age of 60.50 years. Hypertension was the most common co-morbidity. There was no association between stroke location and depression. The incidence of PSD was 30%.

Keywords: post-stroke depression, co-morbidity, disturbance, bilateral

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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: Jinhyun Ryu, Chengliang Xie, Nal Ae Yoon, Dong Hoon Lee, Gu Seob Roh, Hyun Joon Kim, Gyeong Jae Cho, Wan Sung Choi, Sang Soo Kang

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Type 2 diabetes is a heterogeneous group of metabolic disorders featured by a deficit in or loss of insulin activity to maintain normal glucose homeostasis. Mainly, it results from the compromised insulin secretion and/or reduced insulin activity. The frequency of type 2 diabetes (T2D) has been increased rapidly in recent decades with the increase in the trend of obesity due to life style and food habit. Obesity is considered to be the primary risk factor for the development of insulin resistance and thereby developing T2D. Traditionally naturally occurring fruits, vegetables etc. are being used to treat many pathogenic conditions. In this study, we tried to find out the effect of a popularly used vegetable in Bangladesh and several other Asian countries, ‘bitter melon’ on high fat diet induced T2D. To investigate the effect, we used 70% ethanol extract of bitter melon (BME) as dietary supplement with chow. BME was found to attenuate the high fat diet (HFD) induced body weight and total fat mass significantly. We also observed that BME reduced the insulin resistance induced by HFD effectively. Furthermore, dietary supplementation of BME was highly effective in increasing insulin sensitivity, and reducing the hepatic fat and obesity. These results indicate that BME could be effective to attenuate T2D and could be a preventive measure against T2D.

Keywords: bitter melon, obesity, type 2 diabetes, high fat diet

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Authors: Jma Hannan, Prawej Ansari, Yasser H. A. Abdel-Wahab, Peter R. Flatt

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Spirulina platensis (SP, Blue-green algae) have been accepted as a supplement for the treatment of pre and post-diabetes. The present study investigated the effects of butanol fraction from ethanol extract of S. platensis on insulin release from BRIN BD11 cells, isolated mouse islets, and perfused rat pancreas, as well as glucose homeostasis in type 2 diabetic rats and their molecular pathways. In a dose-dependent manner, S. platensis increased insulin release from mouse islets and pancreatic β-cells. The extract also elevated insulin release in perfused rat pancreas. Glucose, isobutylmethylxanthine, tolbutamide, and a depolarizing concentration of KCl significantly potentiated insulin release from BRIN BD11 cells. The effect of diazoxide and verapamil, as well as the absence of extracellular Ca2+ showed a reduction in insulin secretion. When administered orally together with glucose (2.5g/kg bw), S. platensis extract improved fasting and postprandial blood glucose in type 2 diabetes. These data suggest that the anti-diabetic activity of S. platensis is partly mediated by insulin secretion via the KATP channel-dependent pathway/the intracellular cAMP pathway.

Keywords: Insulin, glucose, S. platensis, type 2 diabetes, medicinal plants

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Authors: Y. Mehdipour, S. Ebrahimi, A. Jahanpour, F. Seyedzaei, B. Sabayan, A. Karimi, H. Amirifard

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Ischemic stroke is one of the common reasons for disability and mortality. The fourth leading cause of death in the world and the third in some other sources. Only 1/3 of the patients with ischemic stroke fully recover, 1/3 of them end in permanent disability and 1/3 face death. Thus, the use of predictive models to predict stroke has a vital role in reducing the complications and costs related to this disease. Thus, the aim of this study was to specify the effective factors and predict ischemic stroke with the help of DM methods. The present study was a descriptive-analytic study. The population was 213 cases from among patients referring to Ali ibn Abi Talib (AS) Hospital in Zahedan. Data collection tool was a checklist with the validity and reliability confirmed. This study used DM algorithms of decision tree for modeling. Data analysis was performed using SPSS-19 and SPSS Modeler 14.2. The results of the comparison of algorithms showed that CHAID algorithm with 95.7% accuracy has the best performance. Moreover, based on the model created, factors such as anemia, diabetes mellitus, hyperlipidemia, transient ischemic attacks, coronary artery disease, and atherosclerosis are the most effective factors in stroke. Decision tree algorithms, especially CHAID algorithm, have acceptable precision and predictive ability to determine the factors affecting ischemic stroke. Thus, by creating predictive models through this algorithm, will play a significant role in decreasing the mortality and disability caused by ischemic stroke.

Keywords: data mining, ischemic stroke, decision tree, Bayesian network

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Authors: Min-Ju Jo, Min-Young Um, Moonsung Choi, Sooim Shin

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Type 2 diabetes (T2D) is characterized by insulin resistance, the inability of β-cell and the dysfunction of mitochondria. To characterize effects of Cassia tora extract on mitochondrial dysfunction related T2D, the reduced glutathione level, amount of mitochondrial complexes and activities of mitochondrial complexes were measured. Three groups of mice were modeled; a control group was fed a normal diet, a diabetic group was fed a diabetic diet high in fat and carbohydrates, and a third group was fed a diabetic diet + 70% ethanol extracted Cassia tora seeds for 12 weeks. The amount of mitochondria was determined by Bradford assay after isolation of mitochondria in liver from each group. During isolation of mitochondria, cytosolic fractions of the tissue were collected to measure the reduced glutathione level. Interestingly, high level of the reduced glutathione was observed in Cassia tora treated group and decreased activities of mitochondrial complexes in Cassia tora treated group compared to the diabetic diet group. It indicates that Cassia tora has the potential to increase the reduced form of glutathione functioned as an important antioxidant in cells, and to reduce mitochondrial metabolic compensatory mechanism.

Keywords: antioxidant, Cassia tora, diabetes, electron transport chain, glutathione, mitochondria, spectrophotometry

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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: 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: Hemalatha Ganapathyswamy, Thirukkumar Subramani

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Celiac disease is an autoimmune response to dietary wheat gluten. Gluten is the main structure forming protein in bread and hence developing gluten-free bread is a technological challenge. The study aims at using nonwheat flours like barnyard millet and lentil flour to replace wheat in bread formulations. Other characteristics of these grains, such as high protein, soluble fiber, mineral content and bioactive components make them attractive alternatives to traditional gluten-free ingredients in the production of high protein, gluten-free bread. The composite flour formulations for the development of gluten-free bread were optimized using lentil flour (50 to 70 g), barnyard millet flour (0 to 30 g) and corn flour (0 to 30 g) by means of response surface methodology with various independent variables for physical, sensorial and nutritional characteristics. The optimized composite flour which had a desirability value of 0.517, included lentil flour –62.94 g, barnyard millet flour– 24.34 g and corn flour– 12.72 g with overall acceptability score 8.00/9.00. The optimized gluten-free bread formulation had high protein (14.99g/100g) and fiber (1.95g/100g) content. The glycemic index of the gluten-free bread was 54.58 rendering it as low glycemic which enhances the functional benefit of the gluten-free bread. Since the standardised gluten-free bread from barnyard millet and lentil flour are high protein, and gluten-free with low glycemic index, the product would serve as an ideal therapeutic food in the management of both celiac disease and diabetes mellitus with better nutritional value.

Keywords: gluten free bread, lentil, low glycemic index, response surface methodology

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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: Behcet Al, Şener Cindoruk, Suat Zengin, Mehmet Murat Oktay, Mehmet Mustafa Sunar, Hatice Eroglu, Cuma Yildirim

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Objective: In present study we aimed to investigate the chronic drug use due to chronic diseases in patients admitted to emergency department. Materials-Methods: 144 patients who applied to emergency department (ED) of medicine school of Gaziantep University between June 2013 and September 2013 with chronic diseases and use chronic drugs were included. Information about drugs used by patients were recorded. Results: Of patients, half were male, half were female, and the mean age was 58 years. The first three common diseases were diabetes mellitus, hypertension and coronary artery diseases. Of patients, %79.2 knew their illness. Fifty patients began to use drug within three months, 36 patient began to use within the last one year. While 42 patients brought all of their drugs with themselves, 17 patients brought along a portion of drugs. While three patients stopped their medication completely, 125 patients received medication on a regular basis. Fifty-two patient described the drugs with names, 13 patients described with their colors, 3 patients described by grammes, 45 patients described with the size of the tablet and 13 patients could not describe the drugs. Ninety-two patients explained which kind of drugs were used for each diseases, 17 patient explained partly, and 35 patients had no idea. Hundred patients received medication by themselves, 44 patients medications were giving by their relatives and med carers. Of medications, 140 were written by doctors directly, three medication were given by pharmacist; and one patient bought the drug by himself. For 11 patients the drugs were not harmonious to their diseases. Fifty-one patients admitted to the ED two times within last week, and 73 admitted two times within last month. Conclusion: The majority of patients with chronic diseases and use chronic drugs know their diseases and use the drugs in order, but do not have enough information about their medication.

Keywords: chronic disease, drug use, emergency department, medication

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Authors: Vanessa Bennemann, Gabriela Laste, Márcia Inês Goettert

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The gestational period is a phase in which the pregnant woman undergoes constant physiological and hormonal changes, which are part of the woman’s biological cycle, the development of the fetus, childbirth, and lactation. These are factors of response to the immunological adaptation of the human reproductive process that is directly related to the pregnancy’s well-being and development. Although most pregnancies occur without complications, about 15% of pregnant women will develop potentially fatal complications, implying maternal and fetal risk. Therefore, requiring specialized care for high-risk pregnant women (HRPW) with obstetric interventions for the survival of the mother and/or fetus. Among the risk factors that characterize HRPW are the women's age, gestational diabetes mellitus (GDM), autoimmune diseases, infectious diseases such as syphilis and HIV, hypertension (SAH), preeclampsia, eclampsia, HELLP syndrome, uterine contraction abnormalities, and premature placental detachment (PPD), thyroid disorders, among others. Thus, pregnancy has an impact on the thyroid gland causing changes in the functioning of the mother's thyroid gland, altering the thyroid hormone (TH) profiles and production as pregnancy progresses. Considering, throughout the gestational period, the interpretation of the results of the tests to evaluate the thyroid functioning depends on the stage in which the pregnancy is. Thyroid disorders are directly related to adverse obstetric outcomes and in child development. Therefore, the adequate release of TH is important for a pregnancy without complications and optimal fetal growth and development. Objective: Investigate the physiological effects caused by thyroid disorders in the gestational period. Methods: A search for articles indexed in PubMed, Scielo, and MDPI databases, was performed using the term “AND”, with the descriptors: Pregnancy, Thyroid. With several combinations that included: Melatonin, Thyroidopathy, Inflammatory processes, Cytokines, Anti-inflammatory, Antioxidant, High-risk pregnancy. Subsequently, the screening was performed through the analysis of titles and/or abstracts. The criteria were: including clinical studies in general, randomized or not, in the period of 10 years prior to the research, in the English literature; excluded: experimental studies, case reports, research in the development phase. Results: In the preliminary results, a total of studies (n=183) were found, (n=57) excluded, such as studies of cancer, diabetes, obesity, and skin diseases. Conclusion: To date, it has been identified that thyroid diseases can impair the fetus’s brain development. Further research is suggested on this matter to identify new substances that may have a potential therapeutic effect to aid the gestational period with thyroid diseases.

Keywords: pregnancy, thyroid, melatonin, high-risk pregnancy

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Authors: M. Khaledi Pour, P. Akbartehrani, M. Amini, M. Khani, M. Mohajeri Tehrani, R. Radi, B. Shokri

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Diabetic Foot Ulcer (DFU) is one of the costly severe complications of diabetes. Neuropathy and Peripheral Arterial Disease (PAD) due to diabetes are significant causes of this complication. In 10 years the patients with DFUs are twice as likely to die as patients without DFUs. Cold Atmospheric Plasma (CAP) is a promising tool for medical purposes. CAP generate reactive species at room temperature and are effective in killing bacteria and fibroblast proliferation. These CAP-based tools produce NO, which has bactericidal and angiogenesis properties. It also showed promising effects in the DFUs surface reduction and the time to wound closure. In this paper, we evaluated the effect of the Argon Plasma Jet (APJ) on the healing process of the Wagner Grade 2 DFUs in a randomized clinical trial. The 20 kHz sinusoidal voltage frequency derives the APJ. Patients (n=20) were randomly double-blinded assigned into two groups. These groups receive the standard care (SC, n=10) and the standard care with APJ treatment (SC+APJ, n=10) for five sessions in four weeks. The results showed that the APJ treatment along standard care could reduce the wound surface by 20 percent more than the standard care. Also, It showed a more influential role in controlling wound infection.

Keywords: argon plasma jet, cold atmospheric plasma, diabetes, diabetic foot ulcer

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Authors: Kavita Khoiwal, Vatsla Dadhwal, K. Aparna Sharma, Dipika Deka, Plabani Sarkar

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Introduction: About 2.4 million (1.93 - 3.04 million) people are living with HIV/AIDS in India. Of all HIV infections, 39% (9,30,000) are among women. 5.4% of infections are from mother to child transmission (MTCT), 25,000 infected children are born every year. Besides the risk of mother to child transmission of HIV, these women are at risk of the higher adverse pregnancy outcome. The objectives of the study were to compare the obstetric and neonatal outcome in women who are HIV positive with low-risk HIV negative women and effect of antiretroviral drugs on preterm birth and IUGR. Materials and Methods: This is a retrospective case record analysis of 212 HIV-positive women delivering between 2002 to 2015, in a tertiary health care centre which was compared with 238 HIV-negative controls. Women who underwent medical termination of pregnancy and abortion were excluded from the study. Obstetric outcome analyzed were pregnancy induced hypertension, HIV positive intrauterine growth restriction, preterm birth, anemia, gestational diabetes and intrahepatic cholestasis of pregnancy. Neonatal outcome analysed were birth weight, apgar score, NICU admission and perinatal transmission.HIV-positiveOut of 212 women, 204 received antiretroviral therapy (ART) to prevent MTCT, 27 women received single dose nevirapine (sdNVP) or sdNVP tailed with 7 days of zidovudine and lamivudine (ZDV + 3TC), 15 received ZDV, 82 women received duovir and 80 women received triple drug therapy depending upon the time period of presentation. Results: Mean age of 212 HIV positive women was 25.72+3.6 years, 101 women (47.6 %) were primigravida. HIV positive status was diagnosed during pregnancy in 200 women while 12 women were diagnosed prior to conception. Among 212 HIV positive women, 20 (9.4 %) women had preterm delivery (< 37 weeks), 194 women (91.5 %) delivered by cesarean section and 18 women (8.5 %) delivered vaginally. 178 neonates (83.9 %) received exclusive top feeding and 34 neonates (16.03 %) received exclusive breast feeding. When compared to low risk HIV negative women (n=238), HIV positive women were more likely to deliver preterm (OR 1.27), have anemia (OR 1.39) and intrauterine growth restriction (OR 2.07). Incidence of pregnancy induced hypertension, diabetes mellitus and ICP was not increased. Mean birth weight was significantly lower in HIV positive women (2593.60+499 gm) when compared to HIV negative women (2919+459 gm). Complete follow up is available for 148 neonates till date, rest are under evaluation. Out of these 7 neonates found to have HIV positive status. Risk of preterm birth (P value = 0.039) and IUGR (P value = 0.739) was higher in HIV positive women who did not receive any ART during pregnancy than women who received ART. Conclusion: HIV positive pregnant women are at increased risk of adverse pregnancy outcome. Multidisciplinary team approach and use of highly active antiretroviral therapy can optimize the maternal and perinatal outcome.

Keywords: antiretroviral therapy, HIV infection, IUGR, preterm birth

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Authors: Faten Khanfir, Mohamed Tlili, Ali Medeb Hamrouni, Raki Selmi, M. S. Khalfi, Faten Ben Amor

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Introduction: dental implant failure is a major concern for the clinician and the patient. Objectives: The aim of our study is to investigate the way in which 100 Tunisian dentists carried implant treatment for their patients from the early phase of planning and selection of patients to the placement of the implant in order to look for the implant failure factors. Results: significant correlations were found between failure rates > 5 and their corresponding factors as the number of implants placed (p = 0.001<0, 05), smoking (0.046 <0.05), unbalanced diabetes (0.03<0.05), aseptic protocol (= 0.004< 0.05) and the drilling speed (0,002<0.05) Conclusion: It seems that the number of implant placed, smoking, diabetes, aseptic protocol, and the drilling speed may contribute to dental implant failure.

Keywords: failure, implants, survey, risk, osseointegration

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Authors: Goutam Kumar Ghorai, Sandip Sadhukhan, Arpita Sarkar, Debprasad Sinha, G. Sarkar, Ashis K. Dhara

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Diabetes mellitus is one of the most common chronic diseases in all countries and continues to increase in numbers significantly. Diabetic retinopathy (DR) is damage to the retina that occurs with long-term diabetes. DR is a major cause of blindness in the Indian population. Therefore, its early diagnosis is of utmost importance towards preventing progression towards imminent irreversible loss of vision, particularly in the huge population across rural India. The barriers to eye examination of all diabetic patients are socioeconomic factors, lack of referrals, poor access to the healthcare system, lack of knowledge, insufficient number of ophthalmologists, and lack of networking between physicians, diabetologists and ophthalmologists. A few diabetic patients often visit a healthcare facility for their general checkup, but their eye condition remains largely undetected until the patient is symptomatic. This work aims to focus on the design and development of a fully automated intelligent decision system for screening retinal fundus images towards detection of the pathophysiology caused by microaneurysm in the early stage of the diseases. Automated detection of microaneurysm is a challenging problem due to the variation in color and the variation introduced by the field of view, inhomogeneous illumination, and pathological abnormalities. We have developed aconvolutional neural network for efficient detection of microaneurysm. A loss function is also developed to handle severe class imbalance due to very small size of microaneurysms compared to background. The network is able to locate the salient region containing microaneurysms in case of noisy images captured by non-mydriatic cameras. The ground truth of microaneurysms is created by expert ophthalmologists for MESSIDOR database as well as private database, collected from Indian patients. The network is trained from scratch using the fundus images of MESSIDOR database. The proposed method is evaluated on DIARETDB1 and the private database. The method is successful in detection of microaneurysms for dilated and non-dilated types of fundus images acquired from different medical centres. The proposed algorithm could be used for development of AI based affordable and accessible system, to provide service at grass root-level primary healthcare units spread across the country to cater to the need of the rural people unaware of the severe impact of DR.

Keywords: retinal fundus image, deep convolutional neural network, early detection of microaneurysms, screening of diabetic retinopathy

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Authors: Muhammad Mazhar, Yong Zhu, Likang Qin

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Foods contain endogenous components known as dietary fibers, which are classified into soluble and insoluble forms. Dietary fibers are resistant to gut digestive enzymes, modulating anaerobic intestinal microbiota (AIM) and fabricating short-chain fatty acids (SCFAs). Acetate, butyrate, and propionate dominate in the gut, and different pathways, including Wood-Ljungdahl and acrylate pathways, generate these SCFAs. In pancreatic dysfunction, the release of insulin/glucagon is impaired, which leads to hyperglycemia. SCFAs enhance insulin sensitivity or secretion, beta-cell functions, leptin release, mitochondrial functions, and intestinal gluconeogenesis in human organs, which positively affect type 2 diabetes (T2D). Research models presented that SCFAs either enhance the release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) from L-cells (entero-endocrine) or promote the release of leptin hormone satiation in adipose tissues through G-protein receptors, i.e., GPR-41/GPR-43. Dietary fibers are the components of foods that influence AIM and produce SCFAs, which may be offering beneficial effects on T2D. This review addresses the effectiveness of SCFAs in modulating gut AIM in the fermentation of dietary fiber and their worth against T2D.

Keywords: dietary fibers, intestinal microbiota, short-chain fatty acids, fermentation, type 2 diabetes

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Authors: Md. M. Hossain, Regan Roat, Jenica Christopherson, Colette Free, Zhiguang Guo

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Long noncoding RNA (lncRNA) mediated post-transcriptional gene regulation, and their epigenetic landscapes have been shown to be involved in many human diseases. However, their regulation in diabetes through governing islet’s β-cell function and survival needs to be elucidated. Due to the technical and ethical constraints, it is difficult to study their role in β-cell function and survival in human under in vivo condition. In this study, humanized mice have been developed through transplanting human pancreatic islet under the kidney capsule of NOD.SCID mice and induced β-cell death leading to diabetes condition to study lncRNA mediated regulation. For this, human islets from 3 donors (3000 IEQ, purity > 80%) were transplanted under the kidney capsule of STZ induced diabetic NOD.scid mice. After at least 2 weeks of normoglycecemia, lymphocytes from diabetic NOD mice were adoptively transferred and islet grafts were collected once blood glucose reached > 200 mg/dl. RNA from human donor islets, islet grafts from humanized mice with either adoptive lymphocyte transfer (ALT) or PBS control (CTL) were ribodepleted; barcoded fragment libraries were constructed and sequenced on the Ion Proton sequencer. lncRNA expression in isolated human islets, islet grafts from humanized mice with and without induced β-cell death and their regulation in human islets function in vitro under glucose challenge, cytokine mediated inflammation and induced apoptotic condition were investigated. Out of 3155 detected lncRNAs, 299 that highly expressed in islets were found to be significantly downregulated and 224 upregulated in ALT compared to CTL. Most of these are found to be collocated within 5 kb upstream and 1 kb downstream of 788 up- and 624 down-regulated mRNAs. Genomic Regions Enrichment of Annotations Analysis revealed deregulated and collocated genes are related to pancreas endocrine development; insulin synthesis, processing, and secretion; pancreatitis and diabetes. Many of them, that found to be located within enhancer domains for islet specific gene activity, are associated to the deregulation of known islet/βcell specific transcription factors and genes that are important for β-cell differentiation, identity, and function. RNA sequencing analysis revealed aberrant lncRNA expression which is associated to the deregulated mRNAs in β-cell function as well as in molecular pathways related to diabetes. A distinct set of candidate lncRNA isoforms were identified as highly enriched and specific to human islets, which are deregulated in human islets from donors with different BMIs and with type 2 diabetes. These RNAs show an interesting regulation in cultured human islets under glucose stimulation and with induced β-cell death by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the media of islets cultured with cytokines. Results of this study suggest that the islet specific lncRNAs are deregulated in human islet with β-cell death, hence important in diabetes. These lncRNAs might be important for human β-cell function and survival thus could be used as biomarkers and novel therapeutic targets for diabetes.

Keywords: β-cell, humanized mouse, pancreatic islet, LncRNAs

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