Volume 4.17 | May 7

Pancreatic Cell News 4.17 May 7, 2013
     In this issue: Publications | Reviews | Science News | Industry News | Policy News | Events | Jobs 
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TOP STORY
Nr5a2 Maintains Acinar Cell Differentiation and Constrains Oncogenic Kras-Mediated Pancreatic Neoplastic Initiation
Researchers investigated the role of Nr5a2 in exocrine maintenance, regeneration and Kras driven neoplasia. They showed that Nr5a2 is not required for the development of the pancreatic acinar lineage but is important for maintenance of acinar identity. [Gut] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

DIABETES

Pancreatic Islet Musculature Adapts to Insulin Resistance through Dilation and Not Angiogenesis
To determine if islet vascularization changes in response to insulin resistance, researchers investigated three independent models of insulin resistance: ob/ob, GLUT4+/-, and mice with high-fat diet-induced obesity. Intravital blood vessel labeling and immunocytochemistry revealed a vascular plasticity in which islet vessel area was significantly increased but intra-islet vessel density was decreased as the result of insulin resistance. [Diabetes] Abstract

Development of the Human Pancreas from Foregut to Endocrine Commitment
Researchers studied the expression profiles of key lineage-specific markers to understand differentiation and morphogenetic events during human pancreas development. In addition to revealing a number of disparities in timing between human and mouse development, these data, directly assembled from human tissue, allow combinations of transcription factors to define sequential stages and differentiating pancreatic cell-types. [Diabetes] Abstract

Enhanced Beta Cell Function and Anti-Inflammatory Effect after Chronic Treatment with the Dipeptidyl Peptidase-4 Inhibitor Vildagliptin in an Advanced-Aged Diet-Induced Obesity Mouse Model
To explore the long-term effects of dipeptidyl peptidase-4 inhibition on insulin secretion and beta cell mass, researchers have generated a high-fat diet-induced-obesity model in mice of advanced age. Beta cell function and glucose tolerance were significantly improved by vildagliptin with both diets. [Diabetologia] Abstract | Press Release

Induction of an Antiviral State and Attenuated Coxsackievirus Replication in Type III Interferon Treated Primary Human Pancreatic Islets
Researchers showed that human islets respond to a Coxsackievirus serotype B3 infection by inducing the expression of type III interferons (IFNs). They also demonstrated that islet endocrine cells from non-diabetic individuals express the type III IFN receptor subunits IFNλR1 and IL-10R2. [J Virol] Abstract

Fibroblast Growth Factor Receptor Like-1 (FGFRL1) Interacts with SHP-1 Phosphatase at Insulin Secretory Granules and Induces Beta-Cell ERK1/2 Activation
Researchers determined beta-cell expression of FGFRL1 as well as consequent effects on FGFR1 signaling and biological responses. They confirmed FGFRL1 expression at the plasma membrane and within distinct intracellular granules of both primary beta and βTC3 cells. [J Biol Chem]
Abstract | Full Article

A Self-Defeating Anabolic Program Leads to β Cell Apoptosis in ER Stress-Induced Diabetes via Regulation of Amino Acid Flux
The authors report that chronic ER stress correlated with increased islet protein synthesis and apoptosis in β-cells in vivo. Paradoxically, chronic ER stress in β-cells induced an anabolic transcription program to overcome translational repression by eIF2α phosphorylation. [J Biol Chem] Abstract | Full Article

PANCREATIC CANCER

Heparanase Promotes Lymphangiogenesis and Tumor Invasion in Pancreatic Neuroendocrine Tumors
Scientists investigated the role of heparanase in pancreatic neuroendocrine tumors (PanNETs) using patient samples and the RIP1-Tag2 PanNET-transgenic mouse model. High heparanase expression significantly correlated with more advanced tumor stage, higher tumor grade and the presence of distant metastasis in PanNET patients. [Oncogene] Abstract

Triptolide Induces the Expression of miRNA-142-3p: A Negative Regulator of Heat Shock Protein 70 and Pancreatic Cancer Cell Proliferation
Researchers investigated the mechanism by which triptolide inhibits heat shock protein 70 (HSP70). As microRNAs (miRNAs) are becoming increasingly recognized as negative regulators of gene expression, they tested whether triptolide regulates HSP70 via miRNAs. They showed that triptolide, as well as quercetin but not gemcitabine, upregulated miRNA-142-3p in pancreatic ductal adenocarcinoma cells. [Mol Cancer Ther] Abstract

Ex Vivo Analysis of Pancreatic Cancer-Infiltrating T Lymphocytes Reveals that ENO-Specific Tregs Accumulate in Tumor Tissue and Inhibit Th1/Th17 Effector Cell Functions
Scientists characterized the effector functions of α-enolase (ENO)1-specific T cells isolated from pancreatic cancer patients, and they specifically evaluated the successful role of intra-tumoral T helper 17 (Th17) cells and the inhibitory role of regulatory T (Tregs) cells in respectively promoting or reducing the cancer-specific immune response. [Cancer Immunol Immun] Abstract

Norepinephrine Inhibits the Migratory Activity of Pancreatic Cancer Cells
Pancreatic cancer cells show a reduced migratory activity upon norepinephrine treatment. By means of their three-dimensional, collagen-based cell migration assay, the authors have investigated the signal transduction pathways involved in this phenomenon. They found that this conflicting effect of norepinephrine on pancreatic cancer cells is due to an imbalanced activation of the two pathways that usually mediate a pro-migratory effect of norepinephrine in other tumor cell types. [Exp Cell Res] Abstract

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REVIEWS

Advanced-Stage Pancreatic Cancer: Therapy Options
This review summarizes the current evidence and discusses available treatment options for both locally advanced and metastatic pancreatic adenocarcinoma. [Nat Rev Clin Oncol] Abstract

The Pancreatic β Cell and Type 1 Diabetes: Innocent Bystander or Active Participant?
Use of high-throughput DNA sequencing has allowed geneticists to perform genome-wide association studies to identify novel gene loci associated with type 1 diabetes mellitus. Interestingly, >50% of these genes encode products that are expressed in β cells. These studies, coupled with emerging molecular evidence that β cells are impaired by gain-of-function or loss-of-function of these loci, suggest an active role for the β cell in eliciting its own demise. [Trends Endocrin Met] Abstract

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

SCIENCE NEWS
New Interim Analysis from Observational Study Suggests that Delivery of Insulin via Valeritas’ V-GO Shows Promise in Improving Glycemic Control for Patients with Type 2 Diabetes
Valeritas, makers of the V-Go® insulin delivery device, announced new interim analysis from an observational study that suggest patients with Type 2 diabetes who switched to the V-Go insulin delivery device from their previous baseline treatment experienced potentially significant improved glycemic control and a reduction in total daily insulin dose. [Press release from Valeritas, Inc. discussing research presented at the American Association of Clinical Endocrinologists (AACE) 22nd Annual Scientific and Clinical Congress, Phoenix] Press Release

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INDUSTRY NEWS

Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company Launch Educational Campaign about Emerging Science in Type 2 Diabetes
Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly and Company announced the launch of an educational campaign designed to provide healthcare professionals with a greater understanding of the role sodium glucose co-transporters play in maintaining blood sugar balance, or glucose homeostasis. [Boehringer Ingelheim, Inc.] Press Release

Abide Therapeutics Announces Collaboration with Merck to Develop Novel Therapies for Type 2 Diabetes and Metabolic Diseases
Abide Therapeutics announced that it has entered into a collaboration agreement with Merck, known as MSD outside the U.S. and Canada, to discover, develop and commercialize small-molecule therapies directed against three novel targets to treat metabolic diseases with a focus on type 2 diabetes. [PR Newswire Association LLC] 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 International Society for Stem Cell Research (ISSCR): Stem Cells in Translation
September 15-18, 2013
Florence, Italy


NEW International Society for Stem Cell Research (ISSCR): Stem Cells in Science & Medicine
October 14-17, 2013
Suzhou, China

NEW SELECTBIO CellTech 2014
January 28-29, 2014
San Diego, United States

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

JOB OPPORTUNITIES

NEW Postdoctoral Fellow (Johns Hopkins University School of Medicine)

NEW PhD Positions – Molecular Mechanisms Controlling Acinar Cell Proliferation (University Hospital Zuerich)

PhD Studentship – Obesity and Type 2 Diabetes (German Diabetes Center)

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

Scientist/Specialist – Mitochondrial Function (The Nestlé Institute of Health Sciences)

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

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

Research Associate – Progression and Metastasis of Pancreatic and Breast Cancer (University of North Carolina at Charlotte)


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