Pancreatic Cell News Volume 10.17 | May 7 2019

TOP STORY

Pancreatic Islet Chromatin Accessibility and Conformation Reveals Distal Enhancer Networks of Type 2 Diabetes Risk

Researchers generated a high-resolution map of islet chromatin loops using Hi-C assays in three islet samples and used loops to annotate target genes of islet enhancers defined using ATAC-seq and published ChIP-seq data. They identified candidate target genes for thousands of islet enhancers, and found that enhancer looping was correlated with islet-specific gene expression. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Central and Peripheral Administration of Fibroblast Growth Factor 1 Improves Pancreatic Islet Insulin Secretion in Diabetic Mouse Models

The authors showed for the first time that fibroblast growth factor 1 (FGF1) increased islet insulin secretion in diabetic mouse models. Central and peripheral FGF1 significantly lowered blood glucose in vivo and increased ex vivo islet insulin secretion from diabetic, but not control mice. [Diabetes] Abstract

Vascular Endothelial PDPK1 Plays a Pivotal Role in the Maintenance of Pancreatic Beta Cell Mass and Function in Adult Male Mice

The proportion of pimonidazole-positive islets was significantly increased in knockout mice. mRNA expression levels related to insulin biosynthesis and beta cell function were significantly decreased in islets of knockout mice. [Diabetologia] Abstract | Full Article

The Orai Ca²⁺ Channel Inhibitor CM4620 Targets Both Parenchymal and Immune Cells to Reduce Inflammation in Experimental Acute Pancreatitis

Researchers tested the effects of CM4620 on store-operated Ca²⁺ entry (SOCE), trypsinogen activation, acinar cell death, activation of NFAT and NF-kB, and inflammatory responses in ex vivo and in vivo rodent models of acute pancreatitis and human pancreatic acini. [J Physiol] Abstract

The Role of Membrane Excitability in Pancreatic β-Cell Glucotoxicity

Mouse models of human neonatal diabetes in which K_ATP gain-of-function mutations were expressed in β-cells (K_ATP-GOF) also lost the link between glucose metabolism and excitation-induced insulin secretion, but in this case K_ATP-GOF β-cells were chronically underexcited, with permanently low [Ca²⁺]_i and lack of glucose-dependent insulin secretion. [Sci Rep] Full Article

PANCREATIC CANCER

ATDC Is Required for the Initiation of KRAS-Induced Pancreatic Tumorigenesis

Ataxia-telangiectasia group D-complementing (ATDC) was required for KRAS-driven acinar-ductal metaplasia (ADM) and its progression to pancreatic intraepithelial neoplasia (PanIN). ATDC promoted ADM progression to PanIN through activation of β-catenin signaling and subsequent SOX9 up-regulation. [Genes Dev] Abstract | Press Release

Thrombin Signaling Promotes Pancreatic Adenocarcinoma through PAR-1-Dependent Immune Evasion

Investigators generated and characterized C57Bl/6-derived KPC cell lines. Tissue factor and protease-activated receptor-1 (PAR-1) were highly expressed in primary KPC pancreatic lesions and KPC cell lines similar to expression profiles observed in pancreatic ductal adenocarcinoma patient biopsies. [Cancer Res] Abstract

Zinc Chelator TPEN Induces Pancreatic Cancer Cell Death through Causing Oxidative Stress and Inhibiting Cell Autophagy

The authors found that N,N,N,N-Tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN) markedly induced cell death, via increasing reactive oxygen species (ROS) and restraining autophagy. They also found that TPEN-stimulated mitochondrial metabolism produced much ROS. [J Cell Physiol] Abstract

Rosmarinic Inhibits Cell Proliferation, Invasion and Migration via Up-Regulating miR-506 and Suppressing MMP2/16 Expression in Pancreatic Cancer

Scientists explored the effects of rosmarinic acid on pancreatic progression and explored the underlying molecular mechanisms. Rosmarinic acid significantly suppressed cell viability, cell growth, cell invasion and migration as well as epithelial mesenchymal transition of pancreatic cancer cells, and induced cell apoptosis in pancreatic cells. [Biomed Pharmacother] Full Article

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Adipocyte Metabolism and Insulin Signaling Perturbations: Insights from Genetics

The authors discuss progress towards understanding the molecular mechanisms underlying diseased adipocytes, with an eye towards the future in developing novel therapeutics to combat metabolic disease. [Trends Endocrinol Metab] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

Akcea and Ionis Announce Approval of WAYLIVRA^® (Volanesorsen) in the European Union

Akcea Therapeutics, Inc. and Ionis Pharmaceuticals, Inc. announced that WAYLIVRA has received conditional marketing authorization from the European Commission as an adjunct to diet in adult patients with genetically confirmed familial chylomicronemia syndrome and at high risk for pancreatitis, in whom response to diet and triglyceride lowering therapy has been inadequate. [Akcea Therapeutics, Inc.] Press Release

PharmaCyte Biotech Advances Manufacturing Process for Clinical Trial in Pancreatic Cancer

PharmaCyte Biotech, Inc. announced that advances have been completed in the manufacturing process for the clinical trial product that will be used in PharmaCyte’s planned clinical trial in locally advanced, inoperable pancreatic cancer. [PharmaCyte Biotech, Inc.] Press Release

XBiotech Announces Enrollment Completion, Positive Findings for Bermekimab in Pancreatic Cancer Study

XBiotech Inc. announced enrollment of the final patient into its Phase I study evaluating bermekimab in patients with advanced pancreatic adenocarcinoma and cachexia. [XBiotech, Inc.] Press Release

Stephen O’Rahilly, MD, Named American Diabetes Association’s^® 2019 Banting Medal Recipient for Scientific Achievement

The American Diabetes Association^® (ADA) will present the 2019 Banting Medal for Scientific Achievement, the ADA’s highest honor, to Stephen O’Rahilly, MD. The Banting Medal recognizes significant, long-term contributions to the understanding, treatment or prevention of diabetes. [American Diabetes Association] Press Release

Black Academics Publish One-Fifth of South Africa’s Research

The proportion of scientific articles published by academics in South Africa who are black, colored or of Indian origin has risen almost tenfold since the end of apartheid, to about one-third, finds a report on scholarly publishing in the country. [Nature News] Editorial

White House to Convene Committee to Address Research Obstacles

The leaders of the White House Office of Science and Technology, National Institutes of Health, National Science Foundation, National Institute of Standards and Technology, and the Department of Energy’s science division have formed a committee “to address issues facing the US research community,” President Donald Trump’s administration announced. [The Scientist] Editorial

NEW Keystone Symposia: Integrating Metabolism and Immunity
April 3-7, 2020
Keystone, Colorado, United States

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NEW Professor – Diabetes Research (University of Tennessee Health Science Center)

Postdoctoral Researcher – Islet Biology (University of Wisconsin-Madison)

Postdoctoral Fellowship – Pancreatic Cancer (Oregon Health and Science University)

Postdoctoral Researcher – Exosomes in Atherosclerosis and Cardiovascular Disease (Northern California Institute for Research and Education)

Postdoctoral Fellowship – Regenerative Medicine (Cornell University)

Postdoctoral Research Position – Molecular Biology and Cancer Research (Augusta University)

Postdoctoral Research Affiliate – Pancreatic Cancer Research (Roswell Park)

Clinical Professor – Diabetes (Univesity of Southern Denmark)

Postdoctoral Research Fellow – Type 2 Diabetes and Obesity (Harvard Medical School/Boston Children’s Hospital)

Postdoctoral Fellowship – Regenerative Medicine and Metabolic Biology (Indiana Biosciences Research Institute)

Research Positions – Pancreatic Beta-Cells (Université de Montréal)

Postdoctoral Fellow – Neuroscience and Diabetes (The Child Health Institute of New Jersey)

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