Volume 4.13 | Apr 9

Pancreatic Cell News 4.13 April 9, 2013
     In this issue: Publications | Reviews | Industry News | Policy News | Events | Jobs 
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TOP STORY
Effect of Common Genetic Variants Associated with Type 2 Diabetes and Glycemic Traits on α- and β-Cell Function and Insulin Action in Man
Scientists studied 43 single nucleotide polymorphisms in 4,654 normoglycemic participants from the Finnish population-based PPP-Botnia study. Islet function was assessed, in vivo, by measuring insulin and glucagon concentrations during OGTT, and, in vitro, by measuring glucose stimulated insulin and glucagon secretion from human pancreatic islets. Variants in BCL11A, TSPAN8, and NOTCH2 affected glucagon secretion both in vivo and in vitro. [Diabetes] Abstract

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PUBLICATIONS (Ranked by impact factor of the journal)

DIABETES

Potential of Protein Phosphatase Inhibitor 1 As Biomarker of Pancreatic Beta Cell Injury In Vitro and In Vivo
Investigators proposed protein phosphatase 1, regulatory (inhibitor) subunit 1A (PPP1R1A) as novel biomarker for acute beta cell destruction. LC-MS/MS proteome analysis of FACS-purified beta cells, tissue-comparative Western blotting and immunohistochemistry indicated relatively high molar abundance and selectivity of PPP1R1A in beta cells. [Diabetes] Abstract

Microarray Analysis of Novel Candidate Genes Responsible for Glucose-Stimulated Insulin Secretion in Mouse Pancreatic β Cell Line MIN6
Researchers previously isolated a subclone, MIN6 clone 4, from the parental MIN6 cells, that shows well-regulated insulin secretion in response to glucose, glybenclamide, and KCl, even after prolonged culture. To investigate the molecular mechanisms responsible for preserving glucose-stimulated insulin secretion in this subclone, they compared four groups of MIN6 cells: Pr-LP (parental MIN6, low passage number), Pr-HP (parental MIN6, high passage number), C4-LP (MIN6 clone 4, low passage number), and C4-HP (MIN6 clone 4, high passage number). [PLoS One] Full Article

PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells
The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. [PLoS One] Full Article

Targeted Overexpression of CKI-Insensitive Cyclin-Dependent Kinase 4 Increases Functional β-Cell Number Through Enhanced Self-Replication in Zebrafish
Researchers tested the hypothesis that insufficient activity of cyclin-dependent kinase 4 may be responsible for the low replication rate by ectopically expressing in β-cells a mutant CDK4 (CDK4R24C) that is insensitive to inhibition by cyclin-dependent kinase inhibitors. [Zebrafish] Abstract

GLP-1 Could Improve the Similarity of Insulin-Producing Cells from Human Adipose Tissue-Derived Mesenchymal Stem Cells and Pancreatic Beta Cells in Cellular Ultrastructure and Function
The authors suggested that insulin-producing cells (IPCs) could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. To obtain a better method through which to acquire more similar IPCs, they compared the difference between IPCs of the glucagon-like peptide-1 (GLP-1) group and IPCs of the non-GLP-1 group in the morphological features in cellular level and physiological function. [J Cell Biochem] Abstract

PANCREATIC CANCER

Pancreatic Tumors Escape from Translational Control through 4E-BP1 Loss
Scientists report that pancreas expresses specifically and massively 4E-BP1 (4E-BP2 is nearly undetectable). However, 4E-BP1 expression is extinguished in more than half of the human pancreatic ductal adenocarcinomas. [Oncogene] Abstract

ERK2-Regulated TIMP1 Induces Hyperproliferation of K-Ras G12D-Transformed Pancreatic Ductal Cells
Researchers investigated the specific genes downstream of MAPK-ERK2 responsible for the hyperproliferative abilities of human and murine primary ductal epithelial cells (PDCs) within an extracellular matrix. Compared with control, DNA synthesis and total cell proliferation was significantly increased in human PDCs harboring the pancreatic ductal adenocarcinoma-common p53, Rb/p16INK4a, and K-RasG12D mutations. [Neoplasia]
Abstract | Full Article

Evaluation of the Potential Therapeutic Role of a New Generation of Vitamin D Analog, MART-10, in Human Pancreatic Cancer Cells In Vitro and In Vivo
Scientists investigated the effectiveness and safety of a new generation, less calcemic analog of 1α,25(OH)2D3, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), in BxPC-3 human pancreatic carcinoma cells in vitro and in vivo. [Cell Cycle] Abstract

Stem Cell Marker Nestin Is Critical for TGF Beta1-Mediated Tumor Progression in Pancreatic Cancer
Researchers showed that nestin overexpression in PDAC cells increased cell motility and drove phenotypic changes associated with the epithelial-mesenchymal transition in vitro; conversely, knockdown of endogenous nestin expression reduced the migration rate, and cells reverted to a more epithelial phenotype. [Mol Cancer Res] Abstract | Full Article

Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
Spongiatriol, a marine furanoditerpenoid that was first isolated in the 1970s, is shown here to inhibit Nuclear Factor Kappa B (NFκB) transcriptional activity in a reporter cell line, to reduce levels of phosphorylated (active) NFκB in the AsPC-1 cell line, to have an IC50 for cytotoxicity in the low micromolar range against the AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1 pancreatic cancer cell lines, and to induce moderate but significant apoptosis in both the AsPC-1 and the Panc-1 cell lines. [Mar Drugs] Abstract | Full Article

New: Directed Differentiation of Pluripotent Stem Cells: A Cell Stem Cell Poster

REVIEWS

Cell-Based Therapeutics: The Next Pillar of Medicine
Two decades ago, the pharmaceutical industry – long dominated by small-molecule drugs – was revolutionized by the advent of biologics. Today, biomedicine sits on the cusp of a new revolution: the use of microbial and human cells as versatile therapeutic engines. Here, researchers discuss the promise of this “third pillar” of therapeutics in the context of current scientific, regulatory, economic, and perceptual challenges. [Sci Transl Med] Abstract | Press Release

Autoimmune Pancreatitis
There are two types of autoimmune pancreatitis (AIP). Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. [Gastroenterol Rep] Full Article

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

INDUSTRY NEWS

Pancreatic Cancer Researchers & Advocates from the Pancreatic Cancer Action Network to Join Rally for Medical Research
Researchers and advocates from the Pancreatic Cancer Action Network will join nearly 200 national organizations in demonstrating their concern about the impact of sequestration on cancer research during the Rally for Medical Research on the steps of the Carnegie Library in Washington, D.C. [PR Newswire Association LLC] Press Release

Islet Sciences Receives Notice of Claims Allowance for U.S. Patent Application for New Medications for Treating Diabetes and other Serious Inflammatory Disorders
Islet Sciences, Inc., a biotechnology company engaged in the research, development and commercialization of patented technologies for people with diabetes, announced today the receipt of a Notice of Claims Allowance for its U.S. Patent Application No. 12/036,646. The title of the invention is Lisofylline Analogs and Methods for Use. [Islet Sciences, Inc.] Press Release

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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 NIDDK-NCI Workshop on Pancreatitis-Diabetes-Pancreatic Cancer
June 12-13, 2013
Bethesda, 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 Fellowship – Developmental Biology/Biophysics (University of Copenhagen)

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

Research Associate (Imperial College London – Faculty of Medicine)

Postdoctoral Position – Basic Diabetes Research (Université Libre de Bruxelles)

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

Postdoctoral Fellowship in Diabetes Research – Cellular Metabolism (Lund University)


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