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Pancreatic beta cell proliferation

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
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
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
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
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
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
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
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
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
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
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
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
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
Hao Yu, Hong-Lei Jiang, Dong Xu, Jun-Zhe Jin, Zhe-Ming Zhao, Yan-Dong Ma, Jian Liang
BACKGROUND/AIMS: MafB, a member of the Maf transcription factor family, plays a key role in the regulation of pancreatic alpha and beta cell differentiation. However, its function in the control of cancer cell proliferation remains unknown. METHODS: The mRNA and protein expression levels of MafB in hepatocellular carcinoma tissues and adjacent non-tumor normal specimens were determined by real-time RT-PCR and Western blot, respectively. Report assay was performed to determine whether the regulation of Cyclin D1 by MafB is at the transcriptional level...
2016: Cellular Physiology and Biochemistry
Anaïs Mozar, Hugo Lin, Katoura Williams, Connie Chin, Rosemary Li, Nagesha Guthalu Kondegowda, Andrew F Stewart, Adolfo Garcia-Ocaña, Rupangi Chhaya Vasavada
AIMS/HYPOTHESIS: Finding ways to stimulate the regeneration of endogenous pancreatic beta cells is an important goal in the treatment of diabetes. Parathyroid hormone-related protein (PTHrP), the full-length (1-139) and amino-terminal (1-36) peptides, enhance beta cell function, proliferation, and survival. Therefore, we hypothesize that PTHrP(1-36) has the potential to regenerate endogenous beta cells. METHODS: The partial pancreatectomy (PPx) mouse model of beta cell injury was used to test this hypothesis...
2016: PloS One
İlhan Elmaci, Meric A Altinoz
Pancreatic cancer (PC) and glioblastoma multiforme (GBM) are among the human cancers with worst prognosis which require an urgent need for efficient therapies. Here, we propose to apply to treat both malignancies with a triple combination of drugs, which are already in use for different indications. Recent studies demonstrated a considerable link between risk of PC and diabetes. In experimental models, anti-diabetogenic agents suppress growth of PC, including metformin (M), pioglitazone (P) and lithium (L)...
October 2016: Biochemical Genetics
Marco Fiore, Mauro Ceccanti, Valentina Carito, Luigi Tarani, Giampiero Ferraguti, George N Chaldakov
: Polyphenols are probably the most known and investigated molecules of nutritional interest as micronutrients present in abundance in our diet. Some of the most important food sources of polyphenols in the Mediterranean diet are olives and olive oil. A growing body of evidence from animal models to clinical studies indicates that polyphenol compounds may have neuroprotective effects in several pathologies of the nervous system through the control of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction...
June 26, 2016: Current Medicinal Chemistry
Swati C Asani, Rinku D Umrani, Kishore M Paknikar
AIM: Our earlier study demonstrated antidiabetic activity of zinc oxide nanoparticles (ZON) in diabetic rats. The present study was performed to elucidate its mechanism of antidiabetic action. METHODS: Protein tyrosine phosphatase 1B, protein kinase B and hormone sensitive lipase phosphorylation; glucose transporter 4 translocation and glucose uptake; glucose 6 phosphatase, phosphoenol pyruvate carboxykinase and glucokinase expression; and pancreatic beta cell proliferation were evaluated after ZON treatment to cells...
July 2016: Nanomedicine
Haoyu Wang, Yaxin Lai, Cheng Han, Aihua Liu, Chenling Fan, Hong Wang, Hongmei Zhang, Shuangning Ding, Weiping Teng, Zhongyan Shan
ANGPTL8/betatrophin is a recently discovered hormone, which mainly synthesized and secreted by liver and adipose tissue, playing a critical role in pancreatic beta cell proliferation. Previous studies have suggested that serum ANGPTL8/betatrophin levels are associated with obesity and diabetes mellitus. Here, we evaluated the prospective association between ANGPTL8/betatrophin and the metabolic syndrome from a community-based cohort of 153 adults without metabolic syndrome. After 3.5-year follow-up, we observed an inverse correlation between the baseline ANGPTL8/betatrophin levels and the incidence of metabolic syndrome, even after multivariate adjustments...
2016: Scientific Reports
Francesca Semplici, Angeles Mondragon, Benedict Macintyre, Katja Madeyski-Bengston, Anette Persson-Kry, Sara Barr, Anna Ramne, Anna Marley, James McGinty, Paul French, Helen Soedling, Ryohsuke Yokosuka, Julien Gaitan, Jochen Lang, Stephanie Migrenne-Li, Erwann Philippe, Pedro L Herrera, Christophe Magnan, Gabriela da Silva Xavier, Guy A Rutter
AIMS/HYPOTHESIS: Per-Arnt-Sim kinase (PASK) is a nutrient-regulated domain-containing protein kinase previously implicated in the control of insulin gene expression and glucagon secretion. Here, we explore the roles of PASK in the control of islet hormone release, by generating mice with selective deletion of the Pask gene in pancreatic beta or alpha cells. METHODS: Floxed alleles of Pask were produced by homologous recombination and animals bred with mice bearing beta (Ins1 (Cre); PaskBKO) or alpha (Ppg (Cre) [also known as Gcg]; PaskAKO) cell-selective Cre recombinase alleles...
September 2016: Diabetologia
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