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Pancreatic beta cell proliferation

Vishal Musale, Yasser H A Abdel-Wahab, Peter R Flatt, J Michael Conlon, Maria Luisa Mangoni
Long-standing Type 2 diabetes is associated with loss of both β-cell function and β-cell mass. Peptides derived from the frog-skin host-defense peptide esculentin-1 have been shown to exhibit potent, broad-spectrum antimicrobial activity. The aim of the present study is to determine whether such peptides also show insulinotropic and β-cell protective activities. Esculentin-1a(1-21).NH2 , esculentin-1b(1-18).NH2 , and esculentin-1a(1-14).NH2 produced concentration-dependent stimulations of insulin release from BRIN-BD11 rat clonal β-cells, 1...
March 17, 2018: Amino Acids
Naoyuki Kitao, Akinobu Nakamura, Hideaki Miyoshi, Hiroshi Nomoto, Kiyohiko Takahashi, Kazuno Omori, Kohei Yamamoto, Kyu Yong Cho, Yasuo Terauchi, Tatsuya Atsumi
OBJECTIVE: We investigated whether glucokinase and insulin receptor substrate-2 were required for beta cell proliferation induced by short-term high-fat (HF) diet feeding, as has been shown for long-term HF diet. METHODS: Eight-week-old C57BL/6 J mice were exposed to either a standard chow (SC) or HF diet. After 1 week on the diet, histopathological beta cell proliferation and gene expression in isolated islets were examined. Additionally, 8-week-old beta cell-specific glucokinase haploinsufficient (Gck+/- ) and Irs2 knockout (Irs2-/- ) mice were exposed to either an SC or HF diet...
March 12, 2018: Metabolism: Clinical and Experimental
Isabel González-Mariscal, Rodrigo A Montoro, Máire E Doyle, Qing-Rong Liu, Michael Rouse, Jennifer F O'Connell, Sara Santa-Cruz Calvo, Susan M Krzysik-Walker, Soumita Ghosh, Olga D Carlson, Elin Lehrmann, Yongqing Zhang, Kevin G Becker, Chee W Chia, Paritosh Ghosh, Josephine M Egan
AIMS/HYPOTHESIS: The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells and is coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling in the beta cell. Deciphering the exact function of CB1R in beta cells has been confounded by the expression of this receptor on multiple tissues involved in regulating metabolism. Thus, in models of global genetic or pharmacological CB1R blockade, it is difficult to distinguish the indirect effects of improved insulin sensitivity in peripheral tissues from the direct effects of inhibiting CB1R in beta cells per se...
March 1, 2018: Diabetologia
Nelly Saber, Jennifer E Bruin, Shannon O'Dwyer, Hellen Schuster, Alireza Rezania, Timothy J Kieffer
Pancreatic progenitors derived from human embryonic stem cells (hESCs) are now in clinical trials for insulin replacement in patients with type 1 diabetes. Animal studies indicate the cells can mature into a mixed population of pancreatic endocrine cells including glucose-responsive beta cells several months after implant, but it remains unclear how conditions in the recipient may influence the maturation and ultimately the function of these cells. Here, we investigated the effects of the host sex and pregnancy on the maturation of human Stage 4 (S4) pancreatic progenitor cells and more mature Stage 7 (S7) pancreatic endocrine cells implanted under the kidney capsule of immunodeficient SCID-Beige mice...
February 5, 2018: Endocrinology
Amalia B Gallardo, Ana R Díaz-Marrero, José M de la Rosa, Luis D'Croz, Germán Perdomo, Irene Cózar-Castellano, José Darias, Mercedes Cueto
Two new chloro-furanocembranolides (1, 2) and two new 1,4-diketo cembranolides (3, 4) were isolated from the crude extract of Leptogorgia sp. together with a new seco-furanocembranolide (5) and the known Z-deoxypukalide (6), rubifolide (7), scabrolide D (8) and epoxylophodione (9). Their structures were determined based on spectroscopic evidence. Four compounds: 1, 2, 7 and 8 were found to activate the proliferation of pancreatic insulin-producing (beta) cells.
February 2, 2018: Marine Drugs
Jay S Mishra, Amar S More, Sathish Kumar
Hyperandrogenism is associated with hyperinsulinemia and insulin resistance in adult females. We tested whether androgens dysregulate pancreatic beta cell function to induce hyperinsulinemia through transcriptional regulation of insulin gene (Ins) in the islets. Adult female Wistar rats implanted with dihydrotestosterone (DHT; 7.5-mg, 90-d release) or placebo pellets were examined after 10 weeks. DHT exposure increased plasma DHT levels by 2-fold similar to that in polycystic ovary syndrome in women. DHT exposure induced hyperinsulinemia with increased HOMA-IR index in fasting state and glucose intolerance and exaggerated insulin responses following glucose tolerance test...
January 22, 2018: Biology of Reproduction
Ahmad Abu Turab Naqvi, Gulam Mustafa Hasan, Md Imtaiyaz Hassan
Pancreatic cancer (PC) is the seventh most common cause of cancer-related deaths worldwide that kills more than 300,000 people every year. Prognosis of PC is very poor with a five-year survival rate about 5%. The most common and highly observed type of PC is pancreatic ductal adenocarcinoma (PDAC). It is preceded by the progression of precursor lesions such as Pancreatic Intraepithelial Neoplasia (PanIN), Intraductal Papillary Neoplasm (IPMN) and Mucinous Cystic Neoplasm (MCN). PanIN is the most common among these premalignant lesions...
March 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Ke Xu, Dezhi Bian, Lanxiang Hao, Fei Huang, Min Xu, Jie Qin, Yanmei Liu
Loss of pancreatic β cells is involved in pathogenesis of gestational diabetes mellitus (GDM). Recently, several studies have elucidated the connection between microRNAs (miRNAs) and diabetes mellitus (DM), but the role of miRNAs in GDM remains unclear. The aim of this study was to evaluate the potential functions of miRNAs in GDM and to investigate the underlying mechanisms of action. First, we explored the expression profile of miRNAs in placenta tissue from GDM patients using microarray. Validation analysis was performed in peripheral blood specimens using quantitative reverse transcription PCR (qRT-PCR)...
2017: EXCLI Journal
Wei Zhao, Jaffer A Ajani, Guha Sushovan, N Ochi, Rosa Hwang, Margarete Hafley, Randy L Johnson, Robert S Bresalier, Craig D Logsdon, Zhiqian Zhang, Shumei Song
BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is characterized by activated pancreatic stellate cells (PSCs), abundance of extracellular matrix (ECM), and production of cytokines and chemokines. Galectin 3 (GAL3), a β galactoside-specific lectin, contributes to PDAC development but its effects on the stroma and cytokine production are unclear. METHODS: The effect of recombinant human GAL3 (rGAL3) on activation of PSC, production of cytokines, and ECM proteins were determined by proliferation, invasion, cytokine array, and quantitative PCR...
December 21, 2017: Gastroenterology
Shruti Mohan, Dawood Khan, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
Oxytocin is associated mainly with modulating reproductive function. However, studies suggest that oxytocin also plays a role in endocrine pancreatic function. In the present study, islet expression of oxytocin and its related receptor was confirmed in mouse islets as well as cultured rodent and human beta-cells. Oxytocin significantly stimulated glucose-induced insulin secretion from isolated mouse islets. Similar insulinotropic actions were also observed in rodent BRIN BD11 and human 1.1B4 beta-cells. Positive effects of oxytocin on insulin secretion were almost fully annulled by the oxytocin receptor antagonist, atosiban...
December 20, 2017: Peptides
Chi Kin Wong, Adam K Wade-Vallance, Dan S Luciani, Paul K Brindle, Francis C Lynn, William T Gibson
p300 ( EP300 ) and CBP ( CREBBP ) are transcriptional coactivators with histone acetyltransferase activity. Various β-cell transcription factors can recruit p300/CBP, and thus the coactivators could be important for β-cell function and health in vivo. We hypothesized that p300/CBP contribute to the development and proper function of pancreatic islets. To test this, we bred and studied mice lacking p300/CBP in their islets. Mice lacking either p300 or CBP in islets developed glucose intolerance attributable to impaired insulin secretion, together with reduced α- and β-cell area and islet insulin content...
March 2018: Diabetes
Nadezhda Mironova, Olga Patutina, Evgenyi Brenner, Alexander Kurilshikov, Valentin Vlassov, Marina Zenkova
Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation...
October 3, 2017: Oncotarget
Claire Stewart, Andrea Estrada, Paul Kim, Dong Wang, Yuren Wei, Chris Gentile, Michael Pagliassotti
The unfolded protein response (UPR) is activated in response to impairments of the folding environment in the endoplasmic reticulum (ER). The most conserved arm of the UPR, inositol-requiring ER-to-nucleus signaling protein (IRE1α), has been linked to the regulation of a diverse array of cellular processes including ER-associated degradation, inflammatory signaling, cell proliferation and membrane biogenesis. Recent studies have utilized the selective, small molecule inhibitor, 4μ8c, to examine the role of IRE1α endoribonuclease (RNase) activity in various cell types including multiple myeloma, mouse embryonic fibroblasts and pancreatic beta cells [1-5]...
April 2017: Endoplasmic Reticulum Stress in Diseases
Wilma Tixi-Verdugo, Juan Contreras-Ramos, Gloria Sicilia-Argumedo, Michael S German, Cristina Fernandez-Mejia
During maturation, pancreatic islets achieve their full capacity to secrete insulin in response to glucose, undergo morphological changes in which alpha-cells decrease and beta-cell mass increases, and they acquire the normal alpha- and beta-cell proportion changes that are important for islet functions later in life. In rodents, the first week of postweaning is critical for islet maturation. Multiple studies have documented the detrimental effects of several conditions on pancreatic maturation; however, few studies have addressed the use of pharmacological agents to enhance islet maturation...
October 25, 2017: Journal of Medicinal Food
Selda Gezginci-Oktayoglu, Evren Onay-Ucar, Serap Sancar-Bas, Ayse Karatug-Kacar, Emine S N Arda, Sehnaz Bolkent
Beta cell mass regulation represents a critical issue for understanding and treatment of diabetes. The most important process in the development of diabetes is beta cell death, generally induced by glucotoxicity or glucolipotoxicity, and the regeneration mechanism of new beta cells that will replace dead beta cells is still not fully understood. The aim of this study was to investigate the generation mechanism of new beta cells by considering the compensation phase of type 2 diabetes mellitus. In this study, pancreatic islet derived mesenchymal stem cells (PI-MSCs) were isolated from adult rats and characterized...
May 2018: Journal of Cellular Physiology
Chunyu Bai, Yuhua Gao, Xiangyang Zhang, Wancai Yang, Weijun Guan
Although melatonin has been shown to exhibit a wide variety of biological functions, its effects on promotion of self-renewal in pancreatic stem cells remain unknown. In this study, we incubated murine pancreatic stem cells (PSCs) with various concentrations of melatonin (0.01, 0.1, 1, 10 or 100 μM) to screen for the optimum culture medium for increasing cell proliferation. We found that 10 μM melatonin can significantly increase proliferation and enhance expression of a stem cell marker, nestin, in PSCs via melatonin receptor 2 (MT2)...
October 16, 2017: Artificial Cells, Nanomedicine, and Biotechnology
Shuo Wang, Ying-Ying Chen, Yu-Peng Li, Jun Gu, Shu-Dong Gu, Hai Shi, Xue-Song Li, Xiao-Ning Lu, Xiang Li, Shuang-Long Zhang, Kang-Jun Yu, Kun Liu, Li-Li Ji
Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/β-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and may promote neural progenitor cell and pancreatic β-cell proliferation. The present study found that DISC1 promotes non-small cell lung cancer (NSCLC) cell growth. Western blotting and immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC cell lines and patient tissues. DISC1 expression was negatively associated with phosphorylated (p-) GSK3β, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis...
September 12, 2017: Oncotarget
Gérald J Prud'homme, Yelena Glinka, Merve Kurt, Wenjuan Liu, Qinghua Wang
Systemic gamma-aminobutyric acid (GABA) therapy prevents or ameliorates type 1 diabetes (T1D), by suppressing autoimmune responses and stimulating pancreatic beta cells. In beta cells, it increases insulin secretion, prevents apoptosis, and induces regeneration. It is unclear how GABA mediates these effects. We hypothesized that Klotho is involved. It is a multi-functional protein expressed in the kidneys, brain, pancreatic beta cells, other tissues, and is cell-bound or soluble. Klotho knockout mice display accelerated aging, and in humans Klotho circulating levels decline with age, renal disease and diabetes...
December 2, 2017: Biochemical and Biophysical Research Communications
Ines Bilic-Curcic, Maja C Berkovic
BACKGROUND AND OBJECTIVES: Personalized management of diabetes has become an imperative since majority of monotherapy fails within 3 years of its use. Identifying responders from nonresponders for a certain type of therapy would reduce a period of unsuccessful treatment and minimize health care costs. Incretin therapies, mainly glucagon-like peptide (GLP)-1 receptor agonists (GLP- 1RA) are relatively new glucose-lowering agents which increase insulin and lower glucagon response as well as slow down glucose absorption by acting on gastric emptying...
November 16, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
Xu Han, Hexige Saiyin, Junjie Zhao, Yuan Fang, Yefei Rong, Chenye Shi, Wenhui Lou, Tiantao Kuang
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and malignant neoplasm. The aberrant expression of miR-135b-5p and secreted frizzled-related protein 4 (SFRP4) has been revealed to be involved in various cancers. However, the clinical significance of miR-135b-5p and that of its potential target SFRP4 in PDAC remain to be elucidated. Here, we found that miR-135b-5p was markedly upregulated in pancreatic cancer tissue compared with corresponding adjacent normal tissue, whereas SFRP4 was significantly downregulated...
September 22, 2017: Oncotarget
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