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Diabetes,Islet pancreatic cell

Bahareh Rajaei, Mohammad Massumi, Michael Wheeler
The International Diabetic Federation estimated that 415 million adults currently have diabetes and 318 million adults had impaired glucose tolerance, putting them at high risk of developing diabetes in the future. In Type 1 Diabetes (T1D), the β cells are lost because of autoimmune reactions. Although islet transplantation has been a promising therapy for T1D, it is greatly limited by pancreatic donors. Here, we describe a protocol to generate glucose- responsive pancreatic β-like (GRPβ-L) cells from human-induced pluripotent stem (iPS) cells...
October 18, 2018: Current Protocols in Human Genetics
James Cantley, Aimee Davenport, Laurène Vetterli, Nandor J Nemes, P Tess Whitworth, Ebru Boslem, Le May Thai, Natalie Mellett, Peter J Meikle, Kyle L Hoehn, David E James, Trevor J Biden
AIMS/HYPOTHESIS: Pancreatic beta cells secrete insulin to maintain glucose homeostasis, and beta cell failure is a hallmark of type 2 diabetes. Glucose triggers insulin secretion in beta cells via oxidative mitochondrial pathways. However, it also feeds mitochondrial anaplerotic pathways, driving citrate export and cytosolic malonyl-CoA production by the acetyl-CoA carboxylase 1 (ACC1) enzyme. This pathway has been proposed as an alternative glucose-sensing mechanism, supported mainly by in vitro data...
October 17, 2018: Diabetologia
Wardhana Wardhana, Achmad Rudijanto
Uric acid as the final result of purine bases metabolism. In high level condition, uric acid enters the cell and act as oxidant, and acts as independent risk factor and predicts the incident of type 2 diabetes mellitus (T2DM). It may directly inactivate or through oxidative reaction that lower the nitric oxide (NO) level. Lower NO level will reduce insulin uptake in tissues and reduce in GLUT4 translocation in cell that will effect the blood glucose level. The High level of uric acid or hyperuricemia makes oxidative stress by inducing the production of reactive oxygen species (ROS) which interferes the insulin signalling pathway,creates inflammatory  state that reduced the insulin sensitivity,blood glucose uptake and metabolism, also reducing the insulin production from pancreatic islet cells...
July 2018: Acta Medica Indonesiana
Bruna Andrade Aguiar, Dailiany Orechio, Paula Fratini, Ana Claudia Oliveira Carreira, Patricia Castelucci, Maria Angelica Miglino
The incidence of diabetes mellitus in dogs is increasing in recent years, mainly because of genetic and/or environmental factors, including endocrine disorders (like in humans); failure of suitable control of blood sugar levels, which triggers hyperglycemia; glycosuria and weight loss, which demands the development of innovative treatments to cure or treat this complex disease in dogs. The present study established for the first time a protocol to obtain and characterize cells derived from pancreas of canine fetuses...
October 17, 2018: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Emilie Courty, Adrien Besseiche, Thi Thu Huong Do, Alexandrine Liboz, Fatima Mohamed Aguid, Evans Quilichini, Melissa Buscato, Pierre Gourdy, Jean-François Gautier, Jean-Pierre Riveline, Cécile Haumaitre, Marion Buyse, Bruno Fève, Ghislaine Guillemain, Bertrand Blondeau
Both type 1 and 2 diabetes are characterized by deficient insulin secretion and decreased beta-cell mass. Thus, regenerative strategies to increase beta-cell mass need to be developed. To characterize mechanisms of beta-cell plasticity, we studied a model of severe insulin resistance in the adult mouse and defined how beta cells adapt. Chronic corticosterone (CORT) treatment was given to adult mice and led to rapid insulin resistance and adaptive increased insulin secretion. Adaptive and massive increase of beta-cell mass was observed during treatment up to 8 weeks...
October 16, 2018: Diabetes
Carla Jiménez-Jiménez, Maribel Lara-Chica, Belén Palomares, Juan Antonio Collado, J Lopez-Miranda, Eduardo Muñoz, Marco A Calzado
N-acyl-dopamines are endolipids with neuroprotective, antiinflammatory and immunomodulatory properties. Previously, we showed the ability of these compounds to induce HIF-1α stabilization. Hypoxia and HIF-1α play an important role in the most relevant stages of diabetic pathogenesis. This work analyzes the possible role of these molecules on beta cell differentiation, insulin production and diabetic foot ulcer. Hypoxia response pathway has been characterized in beta-cell differentiation in rat pancreatic acinar cell line and human islet-derived precursor cells...
November 2018: Biochimica et biophysica acta. Molecular cell research
Xinhui Wang, Hong Gao, Wenhui Wu, Enjun Xie, Yingying Yu, Xuyan He, Jin Li, Wanru Zheng, Xudong Wang, Xizhi Cao, Zhuoxian Meng, Ligong Chen, Junxia Min, Fudi Wang
Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion...
October 15, 2018: Protein & Cell
Lu Li, Zongfu Pan, Si Yang, Wenya Shan, Yanyan Yang
Purpose: The number of people with type 2 diabetes (T2D) is growing rapidly worldwide. Islet β-cell dysfunction and failure are the main causes of T2D pathological processes. The aim of this study was to elucidate the underlying pathways and coexpression networks in T2D islets. Materials and methods: We analyzed the differentially expressed genes (DEGs) in the data set GSE41762, which contained 57 nondiabetic and 20 diabetic samples, and developed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Xi Jin, Chenghui Zhang, Lina Gong, Huifang Li, Yan Wang, Qin Li, Hong Li
BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease, which is the result of autoreactive T lymphocytes attack against pancreatic islet β cells. In recent studies, regulatory T cells (Tregs) have been implicated as being part of the process in T1D. CD39 involved in suppression of inflammation, has been shown to be expressed on Tregs. However, the pathological importance of CD39 to memory Tregs population remains unclear. METHODS: We investigate subsets of Tregs with a focus on resting, effector and memory Tregs, and CD39 expression in Tregs were detected...
October 14, 2018: Journal of Diabetes
Claudiane Guay, Janine K Kruit, Sophie Rome, Véronique Menoud, Niels L Mulder, Angelika Jurdzinski, Francesca Mancarella, Guido Sebastiani, Alena Donda, Bryan J Gonzalez, Camilla Jandus, Karim Bouzakri, Michel Pinget, Christian Boitard, Pedro Romero, Francesco Dotta, Romano Regazzi
Type 1 diabetes is an autoimmune disease initiated by the invasion of pancreatic islets by immune cells that selectively kill the β cells. We found that rodent and human T lymphocytes release exosomes containing the microRNAs (miRNAs) miR-142-3p, miR-142-5p, and miR-155, which can be transferred in active form to β cells favoring apoptosis. Inactivation of these miRNAs in recipient β cells prevents exosome-mediated apoptosis and protects non-obese diabetic (NOD) mice from diabetes development. Islets from protected NOD mice display higher insulin levels, lower insulitis scores, and reduced inflammation...
October 5, 2018: Cell Metabolism
Ghasem Barati, Samad Nadri, Ramin Hajian, Ali Rahmani, Hossein Mostafavi, Yousef Mortazavi, Amir Hossein Taromchi
Tissue and stem cell encapsulation andtransplantation were considered as promising tools in the treatment of patients with diabetes mellitus. The aim of this study was to evaluate the effect of microfluidic encapsulation on the differentiation of trabecular meshwork mesenchymal stem cells (TM-MSC), into insulin-producing cells (IPCs) both in vitro and in vivo. The presence of differentiated cells in microfibers (three dimensional [3D]) and tissue culture plates (TCPS; two dimensional [2D]) culture was evaluated by detecting mRNA and protein expression of pancreatic islet-specific markers as well as measuring insulin release of cells in response to glucose challenges...
October 14, 2018: Journal of Cellular Physiology
Clarence C King, Amelia Ann Brown, Irmak Sargin, K M Bratlie, S P Beckman
Fickian diffusion into a core-shell geometry is modeled. The interior core mimics pancreatic Langerhan islets and the exterior shell acts as inert protection. The consumption of oxygen diffusing into the cells is approximated using Michaelis-Menten kinetics. The problem is transformed to dimensionless units and solved numerically. Two regimes are identified, one that is diffusion limited and the other consumption limited. A regression is fit that describes the concentration at the center of the cells as a function of the relevant physical parameters...
October 10, 2018: Journal of Theoretical Biology
Hongxue Shi, Jian Jan, Josiah E Hardesty, K Cameron Falkner, Russell A Prough, Appakalai N Balamurugan, Sri Prakash Mokshagundam, Suresh T Chari, Matthew C Cave
The endocrine disrupting chemicals, polychlorinated biphenyls (PCBs), have been associated with nonalcoholic steatohepatitis (NASH) and diabetes. However, an integrative analysis of the effects of PCBs on the liver and pancreas has never been performed for the two major PCB subtypes, dioxin-like (DL) and nondioxin-like (NDL), and a mixture of NDL/DL PCBs. Therefore, male C57BL/6 J mice fed a control synthetic diet were treated with either a NDL PCB mixture, Aroclor 1260 (20 mg/kg); a single DL PCB congener, PCB 126 (20 μg/kg); a NDL/DL mixture, Aroclor 1260 plus PCB 126; or vehicle control for 2 weeks...
October 9, 2018: Toxicology and Applied Pharmacology
Wu Lv, Jialin Zhang, Ao Jiao, Bowen Wang, Baomin Chen, Jie Lin
It has been proved that human islet amyloid polypeptide (hIAPP), the main constituent of islet amyloid deposition, is one of the important factors which can induce type 2 diabetes or graft failure after islet transplantation. As there is no research on whether resveratrol degrading the amyloid deposition by its special chemical structure or enhancing autophagy had been published, we decided to detect the function of resveratrol in degrading the amyloid deposition in pancreatic beta cells. We established stable hIAPP-INS1 cell line via transfecting INS1 cells by lentivirus that overexpresses hIAPP...
October 12, 2018: Canadian Journal of Physiology and Pharmacology
Seong Keat Cheah, David Halsall, Peter Barker, John Grant, Abraham Mathews, Shyam Seshadri, Singhan Krishnan
A frail 79-year-old lady with dementia presented with a 2-year history of frequent falls. Recurrent hypoglycaemic episodes were diagnosed and treated with continuous glucose infusion in multiple hospital admissions. Hypoadrenalism and hypothyroidism were ruled out. Whilst hypoglycaemic (blood glucose 1.6 mmol/L), both plasma C-peptide and proinsulin concentrations, were inappropriately elevated at 4210 pmol/L (174–960) and >200 pmol/L (0–7) respectively with plasma insulin suppressed at 12 pmol/L (0–180)...
September 24, 2018: Endocrinology, Diabetes & Metabolism Case Reports
Tatiana Danilova, Ilya Belevich, Huini Li, Erik Palm, Eija Jokitalo, Timo Otonkoski, Maria Lindahl
Global lack of mesencephalic astrocyte-derived neurotropic factor (MANF) leads to progressive postnatal loss of β-cells mass and insulin-dependent diabetes in mice. Similarly to Manf -/- mice, embryonic ablation of MANF specifically from the pancreas results in diabetes. In this study, we assessed the importance of MANF for the postnatal expansion of the pancreatic β-cell mass and for adult β-cell maintenance in mice. Detailed analysis of Pdx-1Cre +/- :: Manf fl/fl mice revealed mosaic MANF expression in postnatal pancreases and significant correlation between the number of MANF-positive β-cells and β-cell mass in individual mice...
October 10, 2018: Diabetes
Eunjin Oh, Miwon Ahn, Solomon Afelik, Thomas C Becker, Bart O Roep, Debbie C Thurmond
Syntaxin 4 (Stx4) enrichment in human and mouse islet grafts improves transplant success in reversing STZ-induced diabetes in mice, although the underlying molecular mechanisms remain elusive. Toward further understanding this, human islets and inducible transgenic mice over-expressing Stx4 selectively in the islet β-cells (βTG-Stx4) were challenged with pro-inflammatory stressors in vitro and in vivo. Remarkably, βTG-Stx4 mice resisted multiple-low dose streptozotocin (STZ)-induced loss of β-cell mass and glucose intolerance; under standard conditions glucose tolerance was enhanced, maintaining normal fasting glycemia and insulinemia...
October 10, 2018: Diabetes
Brian Akhaphong, Amber Lockridge, Seokwon Jo, Ramkumar Mohan, Jacob A Wilcox, Cameron R Wing, Jean F Regal, Emilyn U Alejandro
Maternal hypertension during pregnancy is a major risk factor for intrauterine growth restriction (IUGR), which increases susceptibility to cardiovascular and metabolic disease in adulthood through unclear mechanisms. The aim of this study was to characterize pancreatic beta cell area and function in the fetal rat offspring of reduced uterine perfusion pressure (RUPP) model of gestational hypertension. At embryonic day 19.5, RUPP dams exhibited lower body weight, elevated mean blood pressure, reduced litter size, and higher blood glucose compared to sham-operated controls...
October 10, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Alexis M Ceasrine, Eugene E Lin, David N Lumelsky, Radhika Iyer, Rejji Kuruvilla
A better understanding of processes controlling the development and function of pancreatic islets is critical for diabetes prevention and treatment. Here, we reveal a previously unappreciated function for pancreatic β2-adrenergic receptors (Adrb2) in controlling glucose homeostasis by restricting islet vascular growth during development. Pancreas-specific deletion of Adrb2 results in glucose intolerance and impaired insulin secretion in mice, and unexpectedly, specifically in females. The metabolic phenotypes were recapitulated by Adrb2 deletion from neonatal, but not adult, b-cells...
October 10, 2018: ELife
Katarzyna Kornicka, Agnieszka Śmieszek, Jolanta Szłapka-Kosarzewska, Jennifer M Irwin Houston, Michael Roecken, Krzysztof Marycz
Endocrine disorders are becoming an increasing problem in both human and veterinary medicine. In recent years, more and more horses worldwide have been suffering from equine metabolic syndrome (EMS). This metabolic disorder is characterized by pathological obesity, hyperinsulinaemia, hyperglycaemia and insulin resistance. Although metabolic disorders, including diabetes, have been extensively studied, there are still no data on the molecular effects of EMS in horses. Thus, the aim of this study was to evaluate apoptosis, oxidative stress, autophagy and microRNA (miR) expression in multipotent intestinal epithelial stem cells (IECs) and pancreatic islets (PIs) isolated post mortem form healthy and EMS diagnosed horses...
October 8, 2018: International Journal of Molecular Sciences
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