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Pancreatic beta cell proliferation

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https://www.readbyqxmd.com/read/27900263/islet-chrebp-%C3%AE-is-increased-in-diabetes-and-controls-chrebp-%C3%AE-and-glucose-induced-gene-expression-via-a-negative-feedback-loop
#1
Gu Jing, Junqin Chen, Guanlan Xu, Anath Shalev
OBJECTIVE: Carbohydrate-response element-binding protein (ChREBP) is the major transcription factor conferring glucose-induced gene expression in pancreatic islets, liver and adipose tissue. Recently, a novel ChREBP isoform, ChREBP-β, was identified in adipose tissue and found to be also expressed in islets and involved in glucose-induced beta cell proliferation. However, the physiological function of this less abundant β-isoform in the islet, and in diabetes, is largely unknown. The aims of the present study, therefore, were to determine how diabetes affects ChREBP-β and elucidate its physiological role in pancreatic beta cells...
December 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27895310/tgf%C3%AE-1-overexpression-is-associated-with-improved-survival-and-low-tumor-cell-proliferation-in-patients-with-early-stage-pancreatic-ductal-adenocarcinoma
#2
Evan S Glazer, Eric Welsh, Jose M Pimiento, Jamie K Teer, Mokenge P Malafa
The role of transforming growth factor beta-type-1 (TGFβ1) in pancreatic ductal adenocarcinoma (PDAC) progression is stage-dependent. We hypothesized that TGFβ1 expression is associated with survival and proliferation markers in patients with early-stage PDAC. We acquired clinicopathologic, treatment, and mRNA expression data from The Cancer Genome Atlas data set for 106 patients identified with stage I/II PDAC who underwent pancreaticoduodenectomy. Patients were categorized as high expression when mRNA expression was ≥75th percentile for each gene...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27874076/oligofructose-as-an-adjunct-in-treatment-of-diabetes-in-nod-mice
#3
Clement Chan, Colin M Hyslop, Vipul Shrivastava, Andrea Ochoa, Raylene A Reimer, Carol Huang
In type 1 diabetes, restoration of normoglycemia can be achieved if the autoimmune attack on beta cells ceases and insulin requirement is met by the residual beta cells. We hypothesize that an adjunctive therapy that reduces insulin demand by increasing insulin sensitivity will improve the efficacy of an immunotherapy in reversing diabetes. We tested the gut microbiota-modulating prebiotic, oligofructose (OFS), as the adjunctive therapy. We treated non-obese diabetic mice with an immunotherapy, monoclonal anti-CD3 antibody (aCD3), with or without concurrent dietary supplement of OFS...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27861641/pdcd2l-promotes-palmitate-induced-pancreatic-beta-cell-apoptosis-as-a-foxo1-target-gene
#4
Ye Yin, Wei Yong, Jiani Yu, Xu Zhang, Haiyan Lin, Yunxia Zhu, Xiao Han
Transcription factor FoxO1 is a key regulator of the insulin-signaling pathway, and is reported to play important roles in pancreatic β cell differentiation, proliferation, apoptosis and stress resistance. The multifunctional nature of FoxO1 is due to its regulation of various downstream targets. Previous studies in our lab identified potential FoxO1 target genes using the ChIP-DSL technique and one of those genes, Pdcd2l, was selected for further study. We found that the expression of Pdcd2l was increased with palmitate treatment; the luciferase assay result revealed that enhanced Pdcd2l promoter activity was responsible for the elevation of Pdcd2l expression...
2016: PloS One
https://www.readbyqxmd.com/read/27832316/bone-derived-factors-a-new-gateway-to-regulate-glycemia
#5
Nicolas Bonnet
Type 2 diabetes mellitus (T2DM) and osteoporosis are two major disorders which prevalence increases with aging and is predicted to worsen in the coming years. Preclinical investigations suggest common mechanisms implicated in the pathogenesis of both disorders. Recent evidence has established that there is a clear link between glucose and bone metabolism. The emergence of bone as an endocrine regulator through FGF23 and osteocalcin has led to the re-evaluation of the role of bone cells and bone-derived factors in the development of metabolic diseases such as T2DM...
November 10, 2016: Calcified Tissue International
https://www.readbyqxmd.com/read/27813705/increased-proliferation-of-the-pancreatic-duct-gland-compartment-in-type-1-diabetes
#6
Abu Saleh Md Moin, Peter C Butler, Alexandra E Butler
CONTEXT: Pancreatic duct glands (PDGs) have been proposed as a source of regeneration in response to exocrine pancreas injury, and thus may serve as an organ stem cell niche. There is evidence to suggest ongoing beta-cell formation in longstanding type 1 diabetes (T1D), but the source is unknown. OBJECTIVE: To investigate the pancreatic duct gland (PDG) compartment of the pancreas in humans with T1D for evidence of an active regenerative signature (presence of progenitor cells and increased proliferation) and, in particular, as a potential source of beta-cells...
November 4, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27802569/modeling-spatial-distribution-of-oxygen-in-3d-culture-of-islet-beta-cells
#7
John McReynolds, Yu Wen, Xiaofei Li, Jianjun Guan, Sha Jin
Three-dimensional (3D) scaffold culture of pancreatic β-cell has been proven to be able to better mimic physiological conditions in the body. However, one critical issue with culturing pancreatic β-cells is that β-cells consume large amounts of oxygen, and hence insufficient oxygen supply in the culture leads to loss of β-cell mass and functions. This becomes more significant when cells are cultured in a 3D scaffold. In this study, in order to understand the effect of oxygen tension inside a cell-laden collagen culture on β-cell proliferation, a culture model with encapsulation of an oxygen-generator was established...
November 1, 2016: Biotechnology Progress
https://www.readbyqxmd.com/read/27693017/standardized-bovine-colostrum-derivative-impedes-development-of-type-1-diabetes-in-rodents
#8
Ivana Nikolic, Ivana Stojanovic, Milica Vujicic, Paolo Fagone, Katia Mangano, Stanislava Stosic-Grujicic, Ferdinando Nicoletti, Tamara Saksida
Bovine colostrum is a rich source of nutrients and immunologically active components that play a role in conveying passive immunity to the offspring, protection and maturation of new-born's gastrointestinal tract. Colostrum has exerted positive effects in diseases affecting gastrointestinal tract, as well as type 2 diabetes (T2D). However, health-promoting effects in type 1 diabetes have not been reported. The aim of this study was to investigate therapeutic value of oral administration of standardized bovine colostrum derivative (SBCD) in three models of type 1 diabetes (T1D): spontaneously developed T1D in NOD mice and BB-DP rats, and in chemically induced T1D in C57BL/6 mice with multiple low doses of streptozotocin (MLDS)...
September 24, 2016: Immunobiology
https://www.readbyqxmd.com/read/27677765/metabolic-effects-of-orally-administered-small-molecule-agonists-of-gpr55-and-gpr119-in-multiple-low-dose-streptozotocin-induced-diabetic-and-incretin-receptor-knockout-mice
#9
Aine M McKillop, Brian M Moran, Yasser H A Abdel-Wahab, Noella M Gormley, Peter R Flatt
AIMS/HYPOTHESIS: Abnormal cannabidiol (Abn-CBD) and AS-1269574 are potent selective agonists for GPR55 and GPR119, respectively. The present study evaluated the actions and ability of these small-molecule agonists to counteract experimental diabetes in mice. METHODS: Diabetes was induced in NIH Swiss mice by five consecutive daily intraperitoneal injections of 40 mg/(kg body weight) streptozotocin. Diabetic mice received daily oral administration of Abn-CBD or AS-1269574 (0...
September 27, 2016: Diabetologia
https://www.readbyqxmd.com/read/27613695/is-beta-cell-aging-involved-in-the-pathogenesis-of-diabetes
#10
Junping Wen, Ting Xue, Ying Huang, Xiaoyan Chen, Ying Xue, Wei Lin, Lizhen Zhang, Jin Yao, Huibin Huang, Jixing Liang, Liantao Li, Lixiang Lin, Lidan Shi, Liangchun Cai, Zhuangli Zhu, Gang Chen
BACKGROUND: Beta-cells in different stages have different function and capacity of proliferation, regenerative and apoptosis. We conducted this study to investigate whether there are changes in beta-cell phonotype in the development of diabetes to identify potential beta cell targets for preventing the progression of diabetes. METHODS: We conducted a cross-sectional study of pancreatic tissues obtained from 80 patients classified into three groups: 25 type2 diabetes, 25 impaired fasting glucose, and 30 non-diabetes...
September 10, 2016: Journal of Diabetes
https://www.readbyqxmd.com/read/27609771/insulin-promotes-proliferation-and-fibrosing-responses-in-activated-pancreatic-stellate-cells
#11
Jiayue Yang, Richard T Waldron, Hsin-Yuan Su, Aune Moro, Hui-Hua Chang, Guido Eibl, Kevin Ferreri, Fouad R Kandeel, Aurelia Lugea, Ling Li, Stephen J Pandol
Epidemiological studies support strong links between obesity, diabetes, and pancreatic disorders including pancreatitis and pancreatic adenocarcinoma (PDAC). Type 2 diabetes (T2DM) is associated with insulin resistance, hyperglycemia, and hyperinsulinemia, the latter due to increased insulin secretion by pancreatic beta-cells. We reported that high-fat diet-induced PDAC progression in mice is associated with hyperglycemia, hyperinsulinemia, and activation of pancreatic stellate cells (PaSC). We investigated here the effects of high concentrations of insulin and glucose on mouse and human PaSC growth and fibrosing responses...
October 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27578621/role-of-pancreatic-duct-cell-in-beta-cell-neogenesis-a-mini-review-study
#12
Mahsa Zare, Shahdokht Rastegar, Esmaeel Ebrahimi, Azade Roohipoor, Saeed Shirali
Today diabetes mellitus is known as main threatening for health society. Beta cells have pivotal role in energy homeostasis by balance in blood glucose. Proliferation and neogenesis are two factors for preservation of beta cell mass but these have lower rate during adulthood rather than neonatal. Beta cell destruction occurs during diabetes that leads to hyperglycemia. Continues production of beta cell is a therapeutic strategy to keep normal blood glucose and pancreatic duct cell can be one of the sources of new beta cells...
August 27, 2016: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/27576200/activation-of-the-wnt-%C3%AE-catenin-pathway-in-pancreatic-beta-cells-during-the-compensatory-islet-hyperplasia-in-prediabetic-mice
#13
D A Maschio, R B Oliveira, M R Santos, C P F Carvalho, H C L Barbosa-Sampaio, C B Collares-Buzato
The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/β-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active β-catenin associated with significant increases in protein content and gene expression of β-catenin as well as of cyclins D1, D2 and c-Myc (target genes of the Wnt pathway) but not of Tcf7l2 (the transcription factor)...
September 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27568466/microrna-17-92-cluster-regulates-pancreatic-beta-cell-proliferation-and-adaptation
#14
Yaxi Chen, Li Tian, Shan Wan, Ying Xie, Xiang Chen, Xiao Ji, Qian Zhao, Chunyu Wang, Kun Zhang, Janet M Hock, Haoming Tian, Xijie Yu
MiR-17-92 cluster contributes to the regulation of mammalian development, aging and tumorigenesis. The functional roles of miR-17-92 in pancreatic beta-cells are largely unknown. In this study, we found that conditional deletion of miR-17-92 in mouse pancreatic beta-cells (miR-17-92βKO) significantly reduces glucose tolerance and the first phase of insulin secretion, despite normal ad libitum fed and fasting glucose levels. Proliferation is down-regulated in pancreatic beta-cells after deleting miR-17-92. MiR-17-92βKO mice show higher phosphatase and tensin homologue (PTEN) and lower phosphorylated AKT in islets...
December 5, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27562401/impact-of-proton-pump-inhibitor-treatment-on-pancreatic-beta-cell-area-and-beta-cell-proliferation-in-humans
#15
Thomas G K Breuer, Laura Borker, Daniel R Quast, Andrea Tannapfel, Wolfgang E Schmidt, Waldemar Uhl, Juris J Meier
INTRODUCTION: Gastrin has been shown to promote beta-cell proliferation in rodents, but its effects in adult humans are largely unclear. Proton pump inhibitors (PPIs) lead to endogenous hypergastrinaemia, and improved glucose control during PPI therapy has been reported in patients with diabetes. Therefore, we addressed whether PPI treatment is associated with improved glucose homoeostasis, islet cell hyperplasia or increased new beta-cell formation in humans. PATIENTS AND METHODS: Pancreatic tissue specimens from 60 patients with and 33 patients without previous PPI therapy were examined...
November 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27527335/adipose-and-muscle-derived-wnts-trigger-pancreatic-%C3%AE-cell-adaptation-to-systemic-insulin-resistance
#16
Kamil Kozinski, Magdalena Jazurek, Pawel Dobrzyn, Justyna Janikiewicz, Katarzyna Kolczynska, Anna Gajda, Agnieszka Dobrzyn
Wnt signaling molecules are associated with obesity, hyperlipidemia, and type 2 diabetes (T2D). Here, we show that two Wnt proteins, WNT3a and WNT4, are specifically secreted by skeletal muscle and adipose tissue during the development of insulin resistance and play an important role in cross-talk between insulin-resistant tissues and pancreatic beta cells. The activation of Frizzled receptor and Wnt signaling in pancreatic islets via circulating WNT3a in blood resulted in higher insulin secretion and an increase in beta cell proliferation, thus leading to islet adaptation in a pre-diabetic state...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27505464/lipodystrophy-diabetes-and-normal-serum-insulin-in-ppar%C3%AE-deficient-neonatal-mice
#17
Peter E O'Donnell, Xiu Zhen Ye, Melissa A DeChellis, Vannessa M Davis, Sheng Zhong Duan, Richard M Mortensen, David S Milstone
Peroxisome proliferator activated receptor gamma (PPARγ) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPARγ also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPARγ in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPARγ...
2016: PloS One
https://www.readbyqxmd.com/read/27479530/regulation-of-pancreatic-%C3%AE-cell-function-and-proliferation-by-bone-morphogenetic-protein-4-bmp4-in-vitro
#18
Sofie Sylvest Nielsen, Gitte Lund Christensen, Jens Juul Holst, Nils Billestrup
Increased expression of bone morphogenetic proteins (BMPs) in several tissues is associated with inflammation and type 2 diabetes mellitus. BMP2 and BMP4 mRNA expression is increased in pancreatic islets from db/db mice and β-cell proliferation and function are inhibited by BMP4. The effect of BMPs on α-cells is currently unknown. Here, we investigate the effects of BMP4 on mouse and human α-cells in vitro. The effects of BMP4 on α-cell proliferation and function were investigated in islets isolated from male mice and from human donors, and in α-TC1-6 cells...
October 2016: Endocrinology
https://www.readbyqxmd.com/read/27467285/survival-of-autoreactive-t-lymphocytes-by-microrna-mediated-regulation-of-apoptosis-through-trail-and-fas-in-type-1-diabetes
#19
V M de Jong, A R van der Slik, S Laban, R van 't Slot, B P C Koeleman, A Zaldumbide, B O Roep
Autoreactive CD8(+) T cells recognizing autoantigens expressed by pancreatic islets lead to the destruction of insulin-producing beta cells in type 1 diabetes (T1D), but these T cells also occur in healthy subjects. We tested the hypothesis that uncontrolled expansion of diabetogenic T cells in patients occurs, resulting from failure to activate apoptosis. We compared function, transcriptome and epigenetic regulation thereof in relation with fate upon repeated exposure to islet-autoantigen of islet autoreactive T cells from healthy and type 1 diabetic donors with identical islet epitope specificity and HLA-A2 restriction...
September 2016: Genes and Immunity
https://www.readbyqxmd.com/read/27465830/islet-distribution-of-peptide-yy-and-its-regulatory-role-in-primary-mouse-islets-and-immortalised-rodent-and-human-beta-cell-function-and-survival
#20
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
Recent evidence suggests that the classic gut peptide, Peptide YY (PYY), could play a fundamental role in endocrine pancreatic function. In the present study expression of PYY and its NPY receptors on mouse islets and immortalised rodent and human beta-cells was examined together with the effects of both major circulating forms of PYY, namely PYY(1-36) and PYY(3-36), on beta-cell function, murine islet adaptions to insulin deficiency/resistance, as well as direct effects on cultured beta-cell proliferation and apoptosis...
November 15, 2016: Molecular and Cellular Endocrinology
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