Pancreatic Cell News Volume 6.10 | Mar 17 2015

Characterization of Pancreatic NMDA Receptors as Possible Drug Targets for Diabetes Treatment
Researchers found that inhibition of NMDA receptors (NMDARs) in mouse and human islets enhanced their glucose-stimulated insulin secretion and survival of islet cells. Further, NMDAR inhibition prolonged the amount of time that glucose-stimulated beta cells spent in a depolarized state with high cytosolic Ca²⁺ concentrations. [Nat Med] Abstract | Press Release

A Live-Cell, High-Content Imaging Survey of 206 Endogenous Factors across Five Stress Conditions Reveals Context-Dependent Survival Effects in Mouse Primary Beta Cells
Primary mouse islet cells were cultured in conditions mimicking five type 1 or type 2 diabetes-related stresses: basal 5 mmol/L glucose, cytokine cocktail, 1 μmol/L thapsigargin, 1.5 mmol/L palmitate and 20 mmol/L glucose. Scientists surveyed the effects of a library of 206 endogenous factors on islet cell survival through multi-parameter, live-cell imaging. [Diabetologia] Full Article

Unique and Shared Metabolic Regulation in Clonal β-Cells and Primary Islets Derived from Rat Revealed by Metabolomics Analysis
Scientists compared metabolite profiles and gene expression in rat islets and the INS-1 832/13 line, a widely used clonal β-cell model. They found that insulin secretion and metabolic regulation provoked by glucose were qualitatively similar in these β-cell models. [Endocrinology] Abstract

Transcriptional Activity of the Islet β Cell Factor Pdx1 Is Augmented by Lysine Methylation Catalyzed by the Methyltransferase Set7/9
Researchers tested the hypothesis that Lys methylation of Pdx1 by Set7/9 augments Pdx1 transcriptional activity. Cell-based luciferase reporter assays using wild-type and mutant transgenes revealed a requirement of Pdx1 residue K131, but not K123, for transcriptional augmentation by Set7/9. [J Biol Chem]
Abstract | Full Article

Fate Mapping of ptf1a-Expressing Cells during Pancreatic Organogenesis and Regeneration in Zebrafish
To delineate the lineage potential of pancreas transcription factor 1a (ptf1a)-expressing cells, researchers generated ptf1a:creER^T2 transgenic fish and performed genetic-inducible lineage tracing in developmental, regenerating, and ptf1a-deficient zebrafish pancreas. [Dev Dyn] Abstract

PANCREATIC CANCER

SIRT3-Dependent GOT2 Acetylation Status Affects the Malate-Aspartate NADH Shuttle Activity and Pancreatic Tumor Growth
Glutamate oxaloacetate transaminase 2 (GOT2) K159, K185, and K404 (3K) acetylation stimulates NADPH production to suppress ROS and to protect cells from oxidative damage. Moreover, GOT2 3K acetylation promotes pancreatic cell proliferation and tumor growth in vivo. [EMBO J] Abstract | Graphical Abstract

RSpo2 Enhances Canonical Wnt Signaling to Confer Stemness-Associated Traits to Susceptible Pancreatic Cancer Cells
Researchers describe small subpopulations of pancreatic cancer cells with high intrinsic Wnt activity that possess properties indicative of cancer stem cells, including drug-resistance and tumor initiating capacity, while cell populations with negligible Wnt activity preferentially express markers of differentiation. [Cancer Res] Abstract

Embigin Is Overexpressed in Pancreatic Ductal Adenocarcinoma and Regulates Cell Motility through Epithelial to Mesenchymal Transition via the TGF-β Pathway
Scientists transfected BxPC-3 and HPAC pancreatic cancer cells with siRNA or shRNA targeting Embigin and observed reductions in cell proliferation, migration, invasion, wound healing, and reduced levels of matrix metalloproteinases-2 and -9. [Mol Carcinog] Abstract

Oncotropic H-1 Parvovirus Infection Degrades HIF-1α Protein in Human Pancreatic Cancer Cells Independently of VHL and RACK1
Researchers found that infection with the oncolytic H-1 parvovirus decreased HIF-1α protein levels in pancreatic cancer cells under CoCl₂ or hypoxia. [Int J Oncol] Abstract

Aberrant Over-Expression of TRPM7 Ion Channels in Pancreatic Cancer: Required for Cancer Cell Invasion and Implicated in Tumor Growth and Metastasis
Researchers determined the expression levels of transient receptor potential melastatin-subfamily member 7 (TRPM7) in pancreatic tissue microarrays and correlated these measurements in pancreatic adenocarcinoma with the clinicopathological features. They also investigated the role of TRPM7 channels in pancreatic cancer cell invasion using the Matrigel™-coated transwell assay. [Biol Open] Full Article

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The Alliance for Regenerative Medicine Enters into Memorandum of Understanding with Japan’s Forum for Innovative Regenerative Medicine
The Alliance for Regenerative Medicine announced it has entered into a memorandum of understanding with Japan’s Forum for Innovative Regenerative Medicine, effective immediately. [The Alliance for Regenerative Medicine] Press Release

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Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Type 2 Diabetes (Harvard Medical School)

PhD Student Positions – Regenerative Medicine/Stem Cell Biology (University Hospital Tubingen)

Tenure-Track Immunology Faculty Position – Diabetes (University of Connecticut Health Center)

Clinical Research Fellow – Pancreatic Cancer Biology (Cancer Research UK)

Postdoctoral Position – Endothelial Dysfunction and Diabetes (Weill Cornell Medical College in Qatar)

Director – Vector Production (Sangamo BioSciences, Inc.)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Assistant/Associate Professor – Endocrinology, Diabetes and Metabolism Research (University of Pennsylvania)

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