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Pancreatic beta cell proliferation

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https://www.readbyqxmd.com/read/28078385/glucose-and-fatty-acids-synergistically-and-reversibly-promote-beta-cell-proliferation-in-rats
#1
Valentine S Moullé, Kevin Vivot, Caroline Tremblay, Bader Zarrouki, Julien Ghislain, Vincent Poitout
AIMS/HYPOTHESIS: The mechanisms underlying pancreatic islet mass expansion have attracted considerable interest as potential therapeutic targets to prevent or delay the onset of type 2 diabetes. While several factors promoting beta cell proliferation have been identified, in the context of nutrient excess the roles of glucose or NEFA in relation to insulin resistance remain unclear. Here we tested the hypothesis that glucose and NEFA synergistically and reversibly promote beta cell proliferation in the context of nutrient-induced insulin resistance...
January 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28069397/influence-of-neuropeptide-y-and-pancreatic-polypeptide-on-islet-function-and-beta-cell-survival
#2
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
BACKGROUND: In the present study we assessed the impact of neuropeptide Y receptor (NPYR) modulators, neuropeptide Y (NPY) and pancreatic polypeptide (PP), on islet function and beta-cell survival. METHODS: The effects of NPY and PP on beta-cell function were examined in BRIN BD11 and 1.1B4 beta-cells, as well as isolated mouse islets. Involvement of both peptides in pancreatic islet adaptations to streptozotocin and hydrocortisone, as well as effects on beta-cell proliferation and apoptosis was also evaluated...
January 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28067794/the-tgf-%C3%AE-smad4-signaling-pathway-in-pancreatic-carcinogenesis-and-its-clinical-significance
#3
REVIEW
Sunjida Ahmed, Azore-Dee Bradshaw, Shweta Gera, M Zahidunnabi Dewan, Ruliang Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28065853/sitagliptin-inhibit-human-lymphocytes-proliferation-and-th1-th17-differentiation-in-vitro
#4
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
January 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28028036/reduced-islet-function-contributes-to-impaired-glucose-homeostasis-in-fructose-fed-mice
#5
Zeenat A Asghar, Andrew Cusumano, Zihan Yan, Maria S Remedi, Kelle H Moley
Increased sugar consumption, particularly fructose, in the form of sweetened beverages and sweeteners in our diet adversely affects metabolic health. Because these effects are associated with features of the metabolic syndrome in humans, the direct effect of fructose on pancreatic islet function is unknown. We therefore examined the islet phenotype of mice fed excess fructose. Fructose-fed mice exhibited fasting hyperglycemia and glucose intolerance, but not hyperinsulinemia, dyslipidemia, or hyperuricemia...
December 27, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28004148/an-enzymatically-stable-gip-xenin-hybrid-peptide-restores-gip-sensitivity-enhances-beta-cell-function-and-improves-glucose-homeostasis-in-high-fat-fed-mice
#6
Annie Hasib, Ming T Ng, Victor A Gault, Dawood Khan, Vadivel Parthsarathy, Peter R Flatt, Nigel Irwin
AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) and xenin, regulatory gut hormones secreted from enteroendocrine K cells, exert important effects on metabolism. In addition, xenin potentiates the biological actions of GIP. The present study assessed the actions and therapeutic utility of a (DAla(2))GIP/xenin-8-Gln hybrid peptide, in comparison with the parent peptides (DAla(2))GIP and xenin-8-Gln. METHODS: Following confirmation of enzymatic stability, insulin secretory activity of (DAla(2))GIP/xenin-8-Gln was assessed in BRIN-BD11 beta cells...
December 21, 2016: Diabetologia
https://www.readbyqxmd.com/read/28003126/emerging-role-of-hippo-signalling-in-pancreatic-biology-yap-re-expression-and-plausible-link-to-islet-cell-apoptosis-and-replication
#7
REVIEW
Anjana Sharma, Veera Ganesh Yerra, Ashutosh Kumar
Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size...
December 18, 2016: Biochimie
https://www.readbyqxmd.com/read/27960075/a-conserved-bacterial-protein-induces-pancreatic-beta-cell-expansion-during-zebrafish-development
#8
Jennifer Hampton Hill, Eric A Franzosa, Curtis Huttenhower, Karen Guillemin
Resident microbes play important roles in the development of the gastrointestinal tract, but their influence on other digestive organs is less well explored. Using the gnotobiotic zebrafish, we discovered that the normal expansion of the pancreatic β cell population during early larval development requires the intestinal microbiota and that specific bacterial members can restore normal β cell numbers. These bacteria share a gene that encodes a previously undescribed protein, named herein BefA (β Cell Expansion Factor A), which is sufficient to induce β cell proliferation in developing zebrafish larvae...
December 13, 2016: ELife
https://www.readbyqxmd.com/read/27919855/uncoupling-protein-2-deficiency-reduces-proliferative-capacity-of-murine-pancreatic-stellate-cells
#9
Sarah Muller, Sandra Maria Klingbeil, Andreea Sandica, Robert Jaster
BACKGROUND: Uncoupling protein 2 (UCP2) has been suggested to inhibit mitochondrial production of reactive oxygen species (ROS) by decreasing the mitochondrial membrane potential. Experimental acute pancreatitis is associated with increased UCP2 expression, whereas UCP2 deficiency retards regeneration of aged mice from acute pancreatitis. Here, we have addressed biological and molecular functions of UCP2 in pancreatic stellate cells (PSCs), which are involved in pancreatic wound repair and fibrogenesis...
December 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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)...
February 2017: 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
#18
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
#19
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
#20
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
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