Volume 4.06 | Feb 19

Pancreatic Cell News 4.06 February 19, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs 
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TOP STORY
Ras-Related C3 Botulinum Toxin Substrate 1 (RAC1) Regulates Glucose-Stimulated Insulin Secretion via Modulation of F-Actin
The small G-protein ras-related C3 botulinum toxin substrate 1 plays various roles in mammalian cells, such as in the regulation of cytoskeletal organization, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function. [Diabetologia]
Full Article

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PUBLICATIONS (Ranked by impact factor of the journal)

DIABETES

Diabetes Increases Mortality after Myocardial Infarction by Oxidizing CaMKII
Scientists developed a knockin mouse model of oxidation-resistant Ca2+/calmodulin-dependent protein kinase II (ox-CaMKII) (MV-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. [J Clin Invest]
Full Article | Press Release

Regulation of Neurod1 Contributes to the Lineage Potential of Neurogenin3+ Endocrine Precursor Cells in the Pancreas
Researchers investigated where and how the transcription factors Nkx2.2 and Neurod1 genetically interact to differentially regulate endocrine cell specification. [PLoS Genet] Full Article

Species-Specific Vesicular Monoamine Transporter 2 (VMAT2) Expression in Mammalian Pancreatic Beta Cells: Implications for Optimizing Radioligand-Based Human Beta Cell Mass (BCM) Imaging in Animal Models
Since reports on tetrabenazine (TBZ)-based VMAT2 imaging in rodent pancreas have been fraught with confusion, the authors compared VMAT2 gene expression patterns in the mouse, rat, pig and human pancreas, to identify appropriate animal models with which to further validate and optimize TBZ imaging in humans. [Diabetelogia] Abstract

Osteocalcin Reverses Endoplasmic Reticulum Stress and Improves Impaired Insulin Sensitivity Secondary to Diet-Induced Obesity through Nuclear Factor-κB Signaling Pathway
Mice fed a high-fat diet and receiving osteocalcin showed reduced body weight gain, less fat pad gain, and improved insulin sensitivity as well as increased energy expenditure compared with mice fed a high-fat diet and receiving vehicle. Meanwhile, increased endoplasmic reticulum stress, defective insulin signaling, and mitochondrial dysfunction induced by obesity were also effectively alleviated by treatment with osteocalcin. [Endocrinology] Abstract

Regulation of NOX-1 Expression in Beta Cells: A Positive Feedback Loop Involving the Src-Kinase Signaling Pathway
Regulation of NADPH oxidase-1 (NOX-1) expression in beta cells followed modulation of cellular reactive oxygen species (ROS); pro-oxidants increased NOX-1 and anti-oxidants decreased NOX-1. Activation of Src-kinase followed ROS elevation. Inhibition of Src-kinase decreased NOX-1 expression. [Mol Cell Endocrinol] Abstract

PANCREATIC CANCER

Strengthened Glycolysis under Hypoxia Supports Tumor Symbiosis and Hexosamine Biosynthesis in Pancreatic Adenocarcinoma
Using a well-defined mouse model of pancreatic cancer, researchers report that hypoxic areas from pancreatic ductal adenocarcinoma are mainly composed of epithelial cells harboring epithelial-mesenchymal transition features and expressing glycolytic markers, two characteristics associated with tumor aggressiveness. [Proc Natl Acad Sci USA] Abstract

Heparin-Binding Epidermal Growth Factor-Like Growth Factor Eliminates Constraints on Activated Kras to Promote Rapid Onset of Pancreatic Neoplasia
Researchers demonstrated that two oncogenic events, mutation of Kras and production of the growth factor heparin-binding epidermal growth factor-like growth factor, are sufficient for rapid and complete neoplastic transformation of the exocrine pancreas. [Oncogene] Abstract

Protein Kinase Cα Inhibitor Protects against Downregulation of Claudin-1 during Epithelial-Mesenchymal Transition of Pancreatic Cancer
Scientists investigated the mechanisms of regulation of Snail and claudin-1 via a PKCα signal pathway during epithelial-mesenchymal transition in pancreatic cancer cells and in normal human pancreatic duct epithelial cells. [Carcinogenesis] Abstract

Notch Signaling Pathway Targeted Therapy Suppresses Tumor Progression and Metastatic Spread in Pancreatic Cancer
Scientists investigated the in vivo therapeutic effect of PF-03084014, a selective γ-secretase inhibitor, alone and in combination with gemcitabine in pancreatic cancer xenografts. PF-03084014 treatment inhibited the cleavage of nuclear Notch 1 intracellular domain and Notch targets Hes-1 and Hey-1. [Cancer Lett] Abstract

Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy
Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Researchers investigated a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer. [PLoS One] Full Article

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REVIEWS

Senescence in Pancreatic Carcinogenesis: From Signaling to Chromatin Remodeling and Epigenetics
The importance of cellular senescence, a permanent cell growth arrest, is increasingly being recognized as a critical fail-safe programme in pancreatic carcinogenesis. Emerging evidence suggests that oncogene-induced senescence requires transcriptional induction of the CDKN2A gene locus as well as comprehensive chromatin modifications involved in epigenetic silencing of pro-proliferative genes. [Gut] Abstract
INDUSTRY NEWS

ViaCyte Receives More Funding for Diabetes Stem Cell Therapy
JDRF, a global organization focused on type 1 diabetes research, and the California Institute for Regenerative Medicine (CIRM) agreed to provide additional funding for the development of a novel stem cell therapy by ViaCyte. JDRF and CIRM will each contribute $3 million to further advance the project. [ViaCyte, Inc.] Press Release

USC Launches Regenerative Medicine and Stem Cell Research Initiative
A new University of Southern California (USC) initiative has been introduced to support collaborative research in regenerative medicine and stem cell biology across the university, facilitating the critical move from basic research into clinical applications. [University of Southern California] Press Release

POLICY NEWS

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)

EVENTS

NEW American Society of Gene & Cell Therapy (ASGCT) 16th Annual Meeting
May 15-18, 2013
Salt Lake City, United States

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

JOB OPPORTUNITIES

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

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)

Research Position – Diabetes Research (Johns Hopkins University)

Senior Scientist (Spiber Technologies AB)


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