Pancreatic Cell News Volume 4.03 | Jan 29 2013

DIABETES

In Vivo JNK Activation in Pancreatic β-Cells Leads to Glucose Intolerance Caused by Insulin Resistance in Pancreas
Using a transgenic mouse model, investigators showed that c-Jun N-terminal kinase (JNK) activation in β-cells led to glucose intolerance as a result of impaired capacity to increase insulinemia in response to hyperglycemia. [Diabetes] Abstract

Beta Cells Are Not Generated in Pancreatic Duct Ligation Induced Injury in Adult Mice
The authors demonstrated that pancreatic ductal ligation (PDL) does not activate progenitors to contribute to β-cell mass expansion. Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of β-cell content via traditional morphometry methodologies that superficially sample the pancreas. [Diabetes] Abstract

Molecular Basis for the Regulation of Islet Beta Cell Mass in Mice: The Role of E-Cadherin
Scientists hypothesized that increasing levels of E-cadherin during islet formation mediate the decline in beta cell proliferation rate by contributing to a reduction of nuclear β-catenin and D-cyclins. They examined E-cadherin, nuclear β-catenin, and D-cyclin levels, as well as cell proliferation during in vitro and in vivo formation of islet cell aggregates, using β-TC6 cells and transgenic mice with green fluorescent protein-labeled beta cells, respectively. [Diabetologia] Abstract

miRNA-30a-5p-Mediated Silencing of Beta2/NeuroD Expression Is an Important Initial Event of Glucotoxicity-Induced Beta Cell Dysfunction in Rodent Models
Investigators demonstrated that microRNA (miRNA)-30a-5p is a key player in early-stage glucotoxicity-induced beta cell dysfunction. They performed northern blots, RT-PCR and western blots in glucotoxicity-exposed primary rat islets and INS-1 cells. They also measured glucose-stimulated insulin secretion and insulin content. [Diabetologia] Abstract

Hyperplasia of Pancreatic Beta Cells and Improved Glucose Tolerance in Mice Deficient in the FXYD2 Subunit of Na,K-ATPase
Scientists obtained experimental evidence that global knockout of a small, single-span regulatory subunit of Na,K-ATPase, FXYD2, alters glucose control. Adult Fxyd2^-/- mice showed significantly lower blood glucose level, no signs of peripheral insulin resistance, and improved glucose tolerance compared to their littermate controls. [J Biol Chem] Abstract | Full Article

PANCREATIC CANCER

Therapeutic Efficacy of Bifunctional siRNA Combining TGF-β1 Silencing with RIG-I Activation in Pancreatic Cancer
By introducing a triphosphate group at the 5′ end of small interfering RNA (siRNA), gene silencing can be combined with immune activation via the cytosolic helicase retinoic acid-inducible gene I (RIG-I), a ubiquitously expressed receptor recognizing viral RNA. The authors validated RIG-I as a therapeutic target by showing that activation of RIG-I in pancreatic carcinoma cells induced IRF-3 phosphorylation, production of type I interferon, the chemokine CXCL10, as well as caspase-9 mediated tumor cell apoptosis. [Cancer Res] Abstract

Tspan8, CD44v6 and Alpha6Beta4 Are Biomarkers of Migrating Pancreatic Cancer Initiating Cells
Scientists searched for pancreatic adenocarcinoma initiating cell (PaCIC) markers with emphasis on markers contributing to metastatic progression. PaCICs were enriched from long-term and freshly-established lines by repeated selection for spheroid or holoclone growth in advance of evaluating PaCIC markers. [Int J Cancer] Abstract

ICAT Is a Novel PTF1A Interactor that Regulates Pancreatic Acinar Differentiation and Displays Altered Expression in Tumors
Researchers identified ICAT (Inhibitor of ß-Catenin and Tcf4) as a novel Pancreas Transcription Factor 1a (Ptf1a) interactor. ICAT regulates the Wnt pathway and cell proliferation. They validated and mapped the ICAT-Ptf1a interaction in vitro and in vivo, and demonstrated that – upon its overexpression in acinar tumor cells – ICAT negatively regulates PTF1 activity in vitro and in vivo. [Biochem J] Abstract

Neurotransmitter Substance P Mediates Pancreatic Cancer Perineural Invasion via NK-1R in Cancer Cells
This study aimed to determine the relationship between substance P (SP) and pancreatic cancer perineural invasion (PNI) as well as mechanism of SP mediating pancreatic cancer PNI which cause pain in patients with pancreatic cancer. Human pancreatic cancer cells and newborn dorsal root ganglions (DRGs) were used to determine the expression of SP or NK-1R in pancreatic cancer cells and DRGs cells by QT-PCR and Western blotting. [Mol Cancer Res] Abstract

Long-Term Treatment with EXf, a Peptide Analogue of Exendin-4, Improves β-Cell Function and Survival in Diabetic KKAy Mice
Previous studies showed that EXf controls plasma glucose level acting as a glucagon-like peptide 1 receptor agonist. Here the authors evaluated the effects of EXf on β-cell function and survival in diabetic KKAy mice. [Peptides] Abstract

REVIEWS

Autophagy Regulates Inflammation following Oxidative Injury in Diabetes
The authors explore the pathophysiological pathways associated with oxidative stress and inflammation in type 2 diabetes. They also explore how autophagy influences glucose homeostasis by modulating the inflammatory response. [Autophagy] Abstract

Mechanistic Basis of Immunotherapies for Type 1 Diabetes Mellitus
The review summarizes the current information on immunotherapies that aim at modifying T cell response to beta cells. The authors will first outline the immune mechanisms that underlie type 1 diabetes development and progression and review the scientific background and rationale for specific modes of immunotherapy. [Transl Res] Abstract

Threshold Pharmaceuticals Announces Initiation of TH-302 Phase III MAESTRO Study in Patients with Locally Advanced or Metastatic Pancreatic Adenocarcinoma
Threshold Pharmaceuticals, Inc. announced that Threshold’s partner Merck KGaA initiated the global Phase III MAESTRO study assessing the efficacy and safety of investigational hypoxia-targeted drug TH-302 in combination with gemcitabine in patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma. [Threshold Pharmaceuticals, Inc.] Press Release

Salk Institute Awarded Historic $42 Million Grant from the Helmsley Charitable Trust
The Salk Institute for Biological Studies has received a $42 million gift-the largest in the Institute’s history-to establish the Helmsley Center for Genomic Medicine, a research center dedicated to decoding the common genetic factors underlying many complex chronic human diseases. The award, from the Leona M. and Harry B. Helmsley Charitable Trust, will support interdisciplinary research that paves the way to new therapies for chronic illnesses such as cancer, diabetes and Alzheimer’s disease. [Salk Institute for Biological Studies] Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW BIT’s 1^st Annual World Congress of Geriatrics and Gerontology 2013 (WCGG-2013)
October 12-14, 2013
Dalian, China

Visit our events page to see a complete list of events in the pancreatic cell community.

Postdoctoral Position – Diabetes and Beta-Cell Regeneration in Mice (Karolinska Institute)

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

PhD Studentship – Human Pancreatic Beta Cells for Cell Therapy of Diabetes (IDIBELL and University of Barcelona)

Postdoctoral Position – Diabetes Research (Lund University)

Postdoctoral Position – Pancreatic Beta-Cell Dysfunction (Weill Cornell Medical College)

Postdoctoral Position – Diabetes Research (Sanofi-Aventis Deutschland GmbH)

Postdoctoral Position – Pancreas Development (INSERM)

Postdoc Position – Beta Cell Signaling (The University of Southern Denmark)

Postdoctoral Position (Skirball Institute / NYU Medical Center)

PhD Studentship – Developmental Genes in Adult Pancreas Homeostasis & Energy Metabolism (Helmholtz Zentrum München)

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