Pancreatic Cell News Volume 6.42 | Oct 27 2015

Inhibition of DYRK1A and GSK3B Induces Human β-Cell Proliferation
Scientists report aminopyrazine compounds that stimulate robust β-cell proliferation in adult primary islets, most likely as a result of combined inhibition of DYRK1A and GSK3B. Aminopyrazine-treated human islets retain functionality in vitro and after transplantation into diabetic mice. [Nat Commun] Full Article

Feedback Control of Growth, Differentiation, and Morphogenesis of Pancreatic Endocrine Progenitors in an Epithelial Plexus Niche
The authors used EdU pulse-chase and tissue-reconstruction approaches to analyze how endocrine progenitors and their differentiating progeny are assembled within the trunk as it undergoes remodeling from an irregular plexus of tubules to form the eventual mature, branched ductal arbor. [Genes Dev] Abstract

PAX4 Defines an Expandable β-Cell Subpopulation in the Adult Pancreatic Islet
The authors studied mechanisms that allow stringent PAX4 regulation endowing favorable β-cell adaptation in response to changing environment without loss of identity. [Sci Rep] Full Article

Cystine Accumulation Attenuates Insulin Release from the Pancreatic Beta-Cell Due To Elevated Oxidative Stress and Decreased ATP Levels
A Ctns gene knockdown model of cystinosis was developed in the BRIN-BD11 rat clonal pancreatic beta-cell line using Ctns-targeting siRNA. [J Physiol] Abstract

Alcohol and Cigarette Smoke Components Activate Human Pancreatic Stellate Cells: Implications for the Progression of Chronic Pancreatitis
Scientists aimed to determine whether human pancreatic stellate cells (PSCs) and rat PSCs express nicotinic acetylcholine receptors, which are known to bind two important components of cigarette smoke, namely nicotine and nicotine-derived nitrosamine ketone, and examined the effects of cigarette smoke components in the presence and absence of alcohol on PSC activation in vitro. [Alcohol Clin Exp Res] Abstract

PANCREATIC CANCER

IL-1 Receptor Antagonist Inhibits Pancreatic Cancer Growth by Abrogating NF-κB Activation
The authors examined whether targeting interleukin (IL)-1α pathway would inhibit NF-κB activity and thus suppress pancreatic ductal adenocarcinoma cell growth. Human IL-1 receptor antagonist treatment led to a significant decrease in NF-κB activity. [Clin Cancer Res] Abstract

UHRF1 Regulation of the Keap1-Nrf2 Pathway in Pancreatic Cancer Contributes to Oncogenesis
Investigators describe a novel mechanism whereby the epigenetic regulator UHRF1 suppresses Keap1 protein levels. Depletion of UHRF1 from pancreatic ductal adenocarcinoma cells decreased growth, enhanced apoptosis and cell cycle arrest. [J Pathol] Abstract

MiR-652 Inhibits Acidic Microenvironment-Induced Epithelial-Mesenchymal Transition of Pancreatic Cancer Cells by Targeting ZEB1
Researchers found that acidity remarkably enhanced invasion ability of pancreatic cancer (PC) cells accompanying with increased mesenchymal and decreased epithelial markers. MiRNA-microarray showed that miR-652, the potential regulator of ZEB1, was distinctly decreased in acidity-treated PC cells. [Oncotarget] Full Article

SAHA, an HDAC Inhibitor, Overcomes Erlotinib Resistance in Human Pancreatic Cancer Cells by Modulating E-Cadherin
Scientists treated two human pancreatic cancer cell lines with the histone deacetylase inhibitor SAHA. In these Panc-1 and Capan1 cells, they observed that the expression levels of E-cadherin and phosphorylated EGFR were gradually upregulated after treatment with SAHA. [Tumor Biol] Abstract

PKM2 Promotes Cell Survival and Invasion Under Metabolic Stress by Enhancing Warburg Effect in Pancreatic Ductal Adenocarcinoma
Scientists studied the expression pattern and underlying cellular functions of pyruvate kinase isoenzyme M2 (PKM2) in pancreatic ductal adenocarcinoma under metabolic stress. [Dig Dis Sci] Abstract

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TWi Biotechnology Receives Notice of Patent Allowance in Korea for its Lead Drug Candidate AC-201 for the Indication of Type II Diabetes
TWi Biotechnology, Inc. announced that it has received Notice of Allowance for AC-201, TWi Biotechnology’s lead drug candidate, from the Korean Intellectual Property Office for the patent application numbered 10-2012-7029213. This patent includes AC-201 or its pharmaceutically acceptable salts or active metabolites for treatment of both type I and type II diabetes. [TWi Biotechnology, Inc. (PR Newswire Association LLC)] Press Release

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Scientist – Preclinical Immunology (Kanyos Bio)

Postdoctoral Position – Diabetes (University of Geneva Medical School)

Senior Clinical Lecturer – Cancer & Inflammation (Queen Mary University of London)

Research Associate – Pancreatic Cancer Modelling (University College London)

Postdoctoral Fellowship – Action in Obesity and Diabetes Pathogenesis (National Institutes of Health Diabetes)

Postdoctoral Fellow – Diabetes and Metabolism (Johns Hopkins University)

Postdoctoral Position – Pancreatic Cancer (University of California, San Diego)

Postdoctoral Position – Diabetes (Harvard Medical School)

Postdoctoral Research Fellow – Translational Research Program (Fred Hutchinson Cancer Research Center)

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