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Islet production

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https://www.readbyqxmd.com/read/29159187/the-role-of-costimulation-blockade-in-solid-organ-and-islet-xenotransplantation
#1
REVIEW
Kannan P Samy, James R Butler, Ping Li, David K C Cooper, Burcin Ekser
Pig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29157116/perinatal-exposure-to-high-dietary-advanced-glycation-end-products-in-transgenic-nod8-3-mice-leads-to-pancreatic-beta-cell-dysfunction
#2
Danielle J Borg, Felicia Y T Yap, Sahar Keshvari, David G Simmons, Linda A Gallo, Amelia K Fotheringham, Aowen Zhuang, Robyn M Slattery, Sumaira Z Hasnain, Melinda T Coughlan, Phillip Kantharidis, Josephine M Forbes
The contribution of environmental factors to pancreatic islet damage in type 1 diabetes remains poorly understood. In this study, we crossed mice susceptible to type 1 diabetes, where parental male (CD8(+) T cells specific for IGRP206-214; NOD8.3) and female (NOD/ShiLt) mice were randomized to a diet either low or high in AGE content and maintained on this diet throughout pregnancy and lactation. After weaning, NOD8.3(+) female offspring were identified and maintained on the same parental feeding regimen for until day 28 of life...
November 20, 2017: Islets
https://www.readbyqxmd.com/read/29146554/ingap-pp-effects-on-%C3%AE-cell-mass-and-function-are-related-to-its-positive-effect-on-islet-angiogenesis-and-vegfa-production
#3
Carolina Lisi Román, Bárbara Maiztegui, Héctor Del Zotto, Juan José Gagliardino, Luis Emilio Flores
Our aim was to determine whether islet angiogenesis and VEGFA production/release participate in the mechanism by which INGAP-PP enhances β-cell function and mass. We used two models: a) in vivo (normal rats injected with INGAP-PP for 10 days) and b) in vitro (normal islets cultured for 4 days with INGAP-PP, VEGFA, Rapamycin, and the specific VEGF-Receptor inhibitor, SU5416). INGAP-PP administration enhanced insulin secretion, β-cell mass, islet vascularization, and angiogenesis without affecting glucose homeostasis...
November 13, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29132171/metabolic-endotoxemia-activated-macrophages-promote-pancreatic-%C3%AE-cell-death-via-ifn%C3%AE-xaf1-pathway
#4
Mitsudai Tsuruta, Misaki Iwashita, Takanori Shinjo, Hiroaki Matsunaga, Akiko Yamashita, Fusanori Nishimura
Metabolic endotoxemia has been implicated in the pathogenesis of type 2 diabetes. In addition to adipose tissue inflammation, inflammatory cell infiltration is also observed in islets, although its effect on islets is largely unknown. We hypothesized that macrophage infiltration into islets leads to impairment of α or β cell function, which ultimately act to exacerbate the pathophysiology of diabetes. Gene expression in a murine α cell line, αTC1, and β cell line, βTC6, was investigated by DNA microarray after co-culturing the cells with a murine macrophage cell line, RAW 264...
November 13, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29128354/angiotensin-converting-enzyme-2-regulates-mitochondrial-function-in-pancreatic-%C3%AE-cells
#5
Ting-Ting Shi, Fang-Yuan Yang, Chang Liu, Xi Cao, Jing Lu, Xue-Lian Zhang, Ming-Xia Yuan, Chen Chen, Jin-Kui Yang
Mitochondrial metabolism plays an essential role in the regulation of insulin release and glucose homeostasis. Evidence demonstrated that the angiotensin-converting enzyme 2 (ACE2) participates in the regulation of glucose metabolism, however, its role in mitochondrial metabolism remains unclear. The purpose of our study was to determine if ACE2 can regulate mitochondrial function in pancreatic β-cells. We found that ACE2 over-expression restored glucose-stimulated insulin secretion (GSIS) and mitochondrial membrane potential (MMP) in the presence of H2O2 in INS-1 cells...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29118086/creb-crtc2-controls-glp-1-dependent-regulation-of-glucose-homeostasis
#6
Ji-Hyun Lee, Xianlan Wen, Hana Cho, Seung-Hoi Koo
Glucagon-like peptide 1 (GLP-1) is a major incretin that controls glucose homeostasis. The secretion of mature GLP-1 is regulated via GPCRs, including bile acid receptor G protein-coupled bile acid receptor 1, which uses cAMP signaling to enhance the exocytosis of GLP-1-containing vesicles. However, the role of cAMP-mediated transcription has not been clearly demonstrated to date. In this study, we explored the role of cAMP response element-binding protein/CREB-regulated transcription coactivator 2 (CREB/CRTC2)-dependent transcription on GLP-1 secretion in the L cells...
November 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29101297/mesenchymal-stromal-cells-improve-human-islet-function-through-released-products-and-extracellular-matrix
#7
Ahmed A Arzouni, Andreia Vargas-Seymour, Chloe L Rackham, Paramjeet Dhadda, Guo-Cai Huang, Pratik Choudhary, Nance Nardi, Aileen J F King, Peter M Jones
Aims: The aims of the current study were (i) to determine whether the reported beneficial effects of mesenchymal stromal cells (MSCs) on mouse islet function extend to clinically relevant human tissues (islets and MSCs), enabling translation into improved protocols for clinical human islet transplantation; and (ii) to identify possible mechanisms through which human MSCs influence human islet function. Materials and methods: Human islets were co-cultured with human adipose tissue-derived MSCs (hASCs) or pretreated with its products - extracellular matrix (ECM) and annexin A1 (ANXA1)...
November 3, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29101219/mir-204-controls-glucagon-like-peptide-1-receptor-expression-and-agonist-function
#8
SeongHo Jo, Junqin Chen, Guanlan Xu, Truman B Grayson, Lance A Thielen, Anath Shalev
Glucagon-like peptide 1 receptor (GLP1R) agonists are widely used to treat diabetes. However, their function is dependent on adequate GLP1R expression, which is downregulated in diabetes. GLP1R is highly expressed on pancreatic beta cells and activation by endogenous incretin or GLP1R agonists increases cAMP generation, which stimulates glucose-induced beta cell insulin secretion and helps maintain glucose homeostasis. We now have discovered that the highly beta cell-enriched microRNA, miR-204, directly targets the 3'UTR of GLP1R and thereby downregulates its expression in the beta-cell-derived rat INS-1 cell line and primary mouse and human islets...
November 3, 2017: Diabetes
https://www.readbyqxmd.com/read/29095944/mif-inhibition-interferes-with-the-inflammatory-and-t-cell-stimulatory-capacity-of-nod-macrophages-and-delays-autoimmune-diabetes-onset
#9
Hannelie Korf, Laura Breser, Jelter Van Hoeck, Janet Godoy, Dana P Cook, Benoit Stijlemans, Elien De Smidt, Carolien Moyson, João Paulo Monteiro Carvalho Mori Cunha, Virginia Rivero, Conny Gysemans, Chantal Mathieu
Macrophages contribute in the initiation and progression of insulitis during type 1 diabetes (T1D). However, the mechanisms governing their recruitment into the islets as well as the manner of retention and activation are incompletely understood. Here, we investigated a role for macrophage migration inhibitory factor (MIF) and its transmembrane receptor, CD74, in the progression of T1D. Our data indicated elevated MIF concentrations especially in long-standing T1D patients and mice. Additionally, NOD mice featured increased MIF gene expression and CD74+ leukocyte frequencies in the pancreas...
2017: PloS One
https://www.readbyqxmd.com/read/29093682/salidroside-a-natural-antioxidant-improves-%C3%AE-cell-survival-and-function-via-activating-ampk-pathway
#10
Linjie Ju, Xiaohua Wen, Chunjun Wang, Yingjie Wei, Yunru Peng, Yongfang Ding, Liang Feng, Luan Shu
Aim: The enhanced oxidative stress contributes to progression of type 2 diabetes mellitus (T2DM) and induces β-cell failure. Salidroside is a natural antioxidant extracted from medicinal food plant Rhodiola rosea. This study was aimed to evaluate protective effects of salidroside on β-cells against diabetes associated oxidative stress. Methods and Results: In diabetic db/db and high-fat diet-induced mice, we found salidroside ameliorated hyperglycemia and relieved oxidative stress. More importantly, salidroside increased β-cell mass and β-cell replication of diabetic mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29091932/essential-roles-of-aspartate-aminotransferase-1-and-vesicular-glutamate-transporters-in-%C3%AE-cell-glutamate-signaling-for-incretin-induced-insulin-secretion
#11
Naoya Murao, Norihide Yokoi, Kohei Honda, Guirong Han, Tomohide Hayami, Ghupurjan Gheni, Harumi Takahashi, Kohtaro Minami, Susumu Seino
Incretins (GLP-1 and GIP) potentiate insulin secretion through cAMP signaling in pancreatic β-cells in a glucose-dependent manner. We recently proposed a mechanistic model of incretin-induced insulin secretion (IIIS) that requires two critical processes: 1) generation of cytosolic glutamate through the malate-aspartate (MA) shuttle in glucose metabolism and 2) glutamate transport into insulin granules by cAMP signaling to promote insulin granule exocytosis. To directly prove the model, we have established and characterized CRISPR/Cas9-engineered clonal mouse β-cell lines deficient for the genes critical in these two processes: aspartate aminotransferase 1 (AST1, gene symbol Got1), a key enzyme in the MA shuttle, which generates cytosolic glutamate, and the vesicular glutamate transporters (VGLUT1, VGLUT2, and VGLUT3, gene symbol Slc17a7, Slc17a6, and Slc17a8, respectively), which participate in glutamate transport into secretory vesicles...
2017: PloS One
https://www.readbyqxmd.com/read/29089617/low-dose-doxycycline-decreases-systemic-inflammation-and-improves-glycemic-control-lipid-profiles-and-islet-morphology-and-function-in-db-db-mice
#12
Na Wang, Xiong Tian, Yu Chen, Hui-Qi Tan, Pei-Jian Xie, Shao-Jun Chen, Yu-Cai Fu, Yi-Xin Chen, Wen-Can Xu, Chi-Ju Wei
The aim of this study was to determine whether low dose doxycycline as an anti-inflammatory agent could improve glucose metabolism in diabetic animals. Therefore, doxycycline was supplemented in drinking water to 6-week-old male db/db mice for 10 weeks. Doxycycline reduced perirenal/epididymal fat, Lee's index, and liver cholesterol. Blood HDL-cholesterol increased, but total cholesterol and aspartate transaminase decreased. Glucose and insulin tolerances were improved, accompanying with reduced fasting blood glucose, insulin, HOMA-IR and advanced glycation end products...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29083510/on-the-etiology-of-type-1-diabetes-physiological-growth-in-children-impacts-disease-progression
#13
REVIEW
Oskar Skog, Olle Korsgren
The prevailing view is that Type 1 Diabetes (T1D) develops as a consequence of a severe fall in beta-cell mass resulting from T-cell mediated autoimmunity. However, progression from islet autoantibody seroconversion to overt diabetes and finally to total loss of c-peptide production occurs in most affected subjects only slowly over many years or even decades. This slow disease progression should be viewed in relation to the total beta cell mass of only 0.2 - 1.5 g in non-diabetic adults. Focal lesions of acute pancreatitis with accumulation of leukocytes, often located around the ducts, are frequently observed in subjects with recent onset T1D and most patients display extensive periductal fibrosis, the end stage of inflammation...
October 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29073082/transcription-factor-isx-mediates-the-cross-talk-between-diet-and-immunity
#14
Made Airanthi K Widjaja-Adhi, Grzegorz Palczewski, Kali Dale, Elizabeth A Knauss, Mary E Kelly, Marcin Golczak, Alan D Levine, Johannes von Lintig
The intestinal epithelium is a major site for the conversion of dietary β-carotene to retinaldehyde by the enzyme BCO1. The majority of retinaldehyde is further metabolized to retinol (vitamin A), esterified and packaged into triacylglycerol-rich chylomicrons for bodily distribution. Some serve on-site for the synthesis of retinoic acid, a hormone-like compound, which exerts pleiotropic and dominant effects on gastrointestinal immunity. We report here that the intestine-specific homeobox protein ISX is critical to control the metabolic flow of β-carotene through this important branching point of vitamin A metabolism...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29066599/il-6-type-cytokine-signaling-in-adipocytes-induces-intestinal-glp-1-secretion
#15
Stephan Wueest, Céline I Laesser, Marianne Böni-Schnetzler, Flurin Item, Fabrizio C Lucchini, Marcela Borsigova, Werner Müller, Marc Y Donath, Daniel Konrad
We recently showed that IL-6-type cytokine signaling in adipocytes induces FFA release from visceral adipocytes thereby promoting obesity-induced hepatic insulin resistance and steatosis. In addition, IL-6-type cytokines may increase the release of leptin from adipocytes and by that means induce GLP-1 secretion. We thus hypothesized that IL-6-type cytokine signaling in adipocytes may regulate insulin secretion. To this end, mice with adipocyte-specific knockout of gp130, the signal transducer protein of IL-6, were fed a high fat diet for 12 weeks...
October 24, 2017: Diabetes
https://www.readbyqxmd.com/read/29045546/characterization-of-adipose-tissue-product-quality-using-measurements-of-oxygen-consumption-rate
#16
Thomas M Suszynski, David A Sieber, Kathryn Mueller, Allen L Van Beek, Bruce L Cunningham, Jeffrey M Kenkel
Background: Fat grafting is a common procedure in plastic surgery but associated with unpredictable graft retention. Adipose tissue (AT) "product" quality is affected by the methods used for harvest, processing and transfer, which vary widely amongst surgeons. Currently, there is no method available to accurately assess the quality of AT. Objectives: In this study, we present a novel method for the assessment of AT product quality through direct measurements of oxygen consumption rate (OCR)...
October 13, 2017: Aesthetic Surgery Journal
https://www.readbyqxmd.com/read/29033899/environmental-factors-contribute-to-%C3%AE-cell-endoplasmic-reticulum-stress-and-neo-antigen-formation-in-type-1-diabetes
#17
Meghan L Marré, Jon D Piganelli
Type 1 diabetes (T1D) is an autoimmune disease in which immune-mediated targeting and destruction of insulin-producing pancreatic islet β cells leads to chronic hyperglycemia. There are many β cell proteins that are targeted by autoreactive T cells in their native state. However, recent studies have demonstrated that many β cell proteins are recognized as neo-antigens following posttranslational modification (PTM). Although modified neo-antigens are well-established targets of pathology in other autoimmune diseases, the effects of neo-antigens in T1D progression and the mechanisms by which they are generated are not well understood...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29024725/glucagon-a-key-factor-in-the-pathophysiology-of-type-2-diabetes
#18
REVIEW
Jean Girard
Excessive circulating glucagon levels have been reported in all forms of diabetes, clinical or experimental. The hyperglucagonemia of diabetes results from an excessive secretion of the hormone secondary from a deficit in insulin secretion and/or a dysfunction of various cells within the islets of Langerhans (somatostatin) leading to the notion of "paracrinopathy". Hyperglucagonemia contributes to the fasting and postprandial hyperglycemia in diabetic patients through an increased hepatic glucose production (mainly gluconeogenesis)...
October 9, 2017: Biochimie
https://www.readbyqxmd.com/read/29017142/mechanisms-of-antidiabetic-effects-of-flavonoid-rutin
#19
REVIEW
Ahmad Ghorbani
Several lines of evidence suggest that flavonoids that originated from vegetables and medicinal plants have beneficial effects on diabetes by improving glycemic control, lipid profile, and antioxidant status. Rutin is a flavonoid found in many plants and shows a wide range of biological activities including anti-inflammatory, antioxidant, neuroprotective, nephroprotective, and hepatoprotective effects. In this review, the antihyperglycemic property of rutin and its protective effects against the development of diabetic complications are discussed...
October 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28993759/the-four-way-stop-sign-viruses-12-lipoxygenase-islets-and-natural-killer-cells-in-type-1-diabetes-progression
#20
Michele L Semeraro, Lindsey M Glenn, Margaret A Morris
Natural killer (NK) cells represent an important effector arm against viral infection, and mounting evidence suggests that viral infection plays a role in the development of type 1 diabetes (T1D) in at least a portion of patients. NK cells recognize their target cells through a delicate balance of inhibitory and stimulatory receptors on their surface. If unbalanced, NK cells have great potential to wreak havoc in the pancreas due to the beta cell expression of the as-yet-defined NKp46 ligand through interactions with the activating NKp46 receptor found on the surface of most NK cells...
2017: Frontiers in Endocrinology
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