Volume 4.36 | Sep 17

Pancreatic Cell News 4.36 September 17, 2013
Pancreatic Cell News
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2-Aminoadipic Acid Is a Biomarker for Diabetes Risk
In experimental studies, administration of 2-aminoadipic acid (2-AAA) lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. [J Clin Invest] Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Unlimited In Vitro Expansion of Adult Bi-Potent Pancreas Progenitors through the Lgr5/R-Spondin Axis
Wnt signaling is inactive and Lgr5 is not expressed under physiological conditions in the adult pancreas. However, scientists now report that the Wnt pathway is robustly activated upon injury by partial duct ligation, concomitant with the appearance of Lgr5 expression in regenerating pancreatic ducts. [EMBO J]
Full Article | Press Release

Transcription Factor ZBED6 Affects Gene Expression, Proliferation, and Cell Death in Pancreatic Beta Cells
Scientists investigated whether the recently discovered transcription factor, zinc finger BED domain-containing protein 6 (ZBED6), is expressed in insulin-producing cells and, if so, to what extent it affects beta cell function. [Proc Natl Acad Sci USA] Abstract | Full Article

Alternative Splicing and Differential Expression of the Islet Autoantigen IGRP between Pancreas and Thymus Contributes to Immunogenicity of Pancreatic Islets but Not Diabetogenicity in Humans
Investigators tested whether specific splice variation in islets versus thymus correlates with loss of tolerance to islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) in type 1 diabetes. [Diabetologia] Abstract

Pancreatic Duct Ligation after Almost Complete Beta-Cell Loss: Exocrine Regeneration but No Evidence of Beta-Cell Regeneration
There has been great interest in the extent of beta-cell regeneration after pancreatic duct ligation (PDL) and whether alpha-to beta-cell conversion might account for beta-cell regeneration after near-complete beta-cell loss. To assess these questions, scientists established a PDL-model in adult male rats after almost complete beta-cell depletion achieved by giving a single high dose of streptozocin in the fasted state. [Endocrinology] Abstract

Nkx6.1 Is Essential for Maintaining the Functional State of Pancreatic Beta Cells
Given that Nkx6.1 levels are reduced in human type 2 diabetic beta cells, this study lends support to the concept that loss of beta cell features could contribute to the pathogenesis of diabetes. [Cell Rep]
Abstract | Full Article | Graphical Abstract


Genetic Inactivation of Nupr1 Acts as a Dominant Suppressor Event in a Two-Hit Model of Pancreatic Carcinogenesis
Scientists investigated the role of Nupr1 in pancreatic ductal adenocarcinoma progression beyond pancreatic intraepithelial neoplastic lesions in Pdx1-cre;LSL-KrasG12D;Ink4a/Arffl/fl(KIC) mice. [Gut] Abstract

Targeting of NAD Metabolism in Pancreatic Cancer Cells: Potential Novel Therapy for Pancreatic Tumors
Scientists used human pancreatic cancer cells both in vitro and in vivo to demonstrate the role of NAD synthesis and degradation in tumor cell metabolism and growth. They demonstrated that pharmacological and genetic targeting of Nampt, the key enzyme in the NAD salvage synthesis pathway, inhibits cell growth and survival of pancreatic cancer cells. [Clin Cancer Res] Abstract | Full Article

Combination of siRNA-Directed Kras Oncogene Silencing and Arsenic-Induced Apoptosis Using a Nanomedicine Strategy for the Effective Treatment of Pancreatic Cancer
Down-regulation of the mutant Kras gene by siRNA caused defective abilities of proliferation, clonal formation, migration, and invasion of pancreatic cancer cells, as well as cell cycle arrest at the G0/G1 phase, which substantially enhanced the apoptosis-inducing effect of arsenic administration. [Nanomedicine] Abstract

miR-204 Mediated Loss of Myeloid Cell Leukemia-1 Results in Pancreatic Cancer Cell Death
Using pancreatic cancer cell lines, researchers have shown that miR-204, a putative regulator of Mcl-1, is repressed in cancer cell lines compared to normal cells. [Mol Cancer] Abstract | Full Article

Downregulation of Gas5 Increases Pancreatic Cancer Cell Proliferation by Regulating CDK6
Researchers assayed the expression level of gas5 in pancreatic cancer tissues and define the role of gas5 in the regulation of pancreatic cancer cell proliferation. They verified that the expression level of gas5 is significantly decreased in pancreatic cancer tissues compared with normal control. [Cell Tissue Res] Abstract

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New Opportunities: Harnessing Induced Pluripotency for Discovery in Diabetes and Metabolism
The authors highlight the uses of human induced pluripotent stem cells to uncover the underlying causes and pathological consequences of diabetes and metabolic syndromes, multifactorial diseases whose etiologies have been difficult to unravel using traditional methodologies. [Cell Metab] Abstract

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Vanderbilt University Tracking Drug’s Ability to Prevent Type 1 Diabetes
Vanderbilt’s Eskind Diabetes Clinic has been selected to examine the ability of the drug abatacept to prevent type 1 diabetes (T1D). As part of the TrialNet consortium, Vanderbilt will be one of 14 North American sites observing the effects of the drug in people at high risk to develop T1D. [Vanderbilt University] Press Release

Duke University Medical Center Joins Precision Biologics as a Collaborator on Phase IIB Pancreatic Cancer Trial
Precision Biologics announced the addition of Duke University Medical Center as a collaborator on its ongoing Phase IIb clinical trial with its lead therapeutic compound NPC-1C. [Precision Biologics, Inc.]
Press Release

OHSU Launches $25 Million Clinical and Translational Science Initiative against Lethal, Hard-to-Treat Pancreatic Disease
Oregon Health & Science University (OHSU) has launched a clinical and translational science initiative. With support from a landmark $25 million philanthropic pledge, a team of OHSU’s top pancreatic surgeons and Knight Cancer Institute scientists will co-develop new detection and treatment methods for pancreatic cancer while solving longstanding mysteries of pancreatic disease at the molecular level. [Oregon Health & Science University] Press Release

NewLink Genetics Completes Patient Enrollment in Phase III Algenpantucel-L (IMPRESS) Clinical Study
NewLink Genetics Corporation announced that a major milestone has been reached in the IMPRESS (Immunotherapy for Pancreatic Resectable cancer Survival Study) Phase III clinical trial of algenpantucel-L. The accrual goal of 722 subjects with surgically resected pancreatic cancer has been met. The study examines the lead product candidate from NewLink’s proprietary HyperAcuteTM immunotherapy platform, algenpantucel-L, which is designed to stimulate the human immune system to recognize and attack cancer cells. [NewLink Genetics Corporation] Press Release

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NEW Postdoctoral Researcher – Molecular Mechanisms of Innate Immunity and Inflammation (University of North Carolina at Chapel Hill)

Postdoctoral Researcher – Pancreatic Cancer (UT Southwestern Medical Center at Dallas)

Postdoctoral Fellow – Molecular Mechanisms of Cardiovascular Diseases (University of Rochester Medical Center)

Postdoctoral Position – Mechanism of Pancreatic Beta Cell Proliferation (Joslin Diabetes Center/Harvard Medical School)

Postdoctoral Fellow – Pancreatic Beta Cell Regeneration and Survival (Oklahoma Medical Research Foundation)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Postdoctoral Researcher (The University of Texas Health Science Center at San Antonio)

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