Volume 4.42 | Oct 29

Pancreatic Cell News 4.42 October 29, 2013
Pancreatic Cell News
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SH2B1 in ß Cells Regulates Glucose Metabolism by Promoting ß Cell Survival and Islet Expansion
Researchers identified SH2B1, which is highly expressed in ß cells, as a novel regulator of ß cell expansion. Silencing of SH2B1 in INS-1 832/13 ß cells attenuated insulin- and IGF-1-stimulated activation of the PI 3-kinase/Akt pathway and increased streptozotocin-induced apoptosis; conversely, overexpression of SH2B1 had the opposite effects. [Diabetes] Abstract
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PUBLICATIONS ( Ranked by impact factor of the journal)

OATP1B3 Is Expressed in Pancreatic ß-Islet Cells and Enhances the Insulinotropic Effect of the Sulfonylurea Derivative Glibenclamide
Scientists report expression of OATP1B3 in human pancreatic tissue, with the abundance of the transporter localized in the islets of Langerhans. Transport studies using OATP1B3 overexpressing MDCKII cells revealed significant inhibition of the cellular uptake of the known substrate CCK-8 in presence of the insulinotropic anti-diabetic compounds tolbutamide, glibenclamide, glimepiride, and nateglinide, and identified glibenclamide as a novel substrate of OATP1B3. [Diabetes] Abstract

Lysosomal Acid Lipase and Lipophagy Are Constitutive Negative Regulators of Glucose-Stimulated Insulin Secretion from Pancreatic Beta Cells
Scientists aimed to elucidate a role for lysosomal acid lipase (LAL) and lipophagy in pancreatic beta cells. Insulin secretion was increased following chronic inhibition of LAL. This was more pronounced with glucose than with non-nutrient stimuli and was accompanied by augmentation of neutral lipid species. [Diabetologia] Abstract | Press Release

Increased Expression of miR-187 in Human Islets from Individuals with Type 2 Diabetes Is Associated with Reduced Glucose-Stimulated Insulin Secretion
Global TaqMan arrays and individual TaqMan assays were used to measure islet microRNA (miRNA) expression in discovery and replication cohorts from individuals with and without type 2 diabetes. The role of specific dysregulated miRNAs in regulating insulin secretion, content and apoptosis was subsequently investigated in primary rat islets and INS-1 cells. [Diabetologia] Full Article

Keratin 8 Modulates ß-Cell Stress Responses and Normoglycemia
The impact of keratins on ß-cell organization and systemic glucose control was assessed using keratin 8 (K8) wild-type and K8 knockout mice. Islet ß-cell keratins were characterized under basal conditions, in streptozotocin-induced diabetes and in non-obese diabetic mice. [J Cell Sci] Abstract

Transplantation of Insulin-Secreting Cells Differentiated from Human Adipose Tissue-Derived Stem Cells into Type 2 Diabetes Mice
Researchers evaluated the efficacy of cell therapy using insulin-secreting cells differentiated from human eyelid adipose tissue-derived stem cells into type 2 diabetes mice. [Biochem Biophys Res Commun] Abstract


Glycolytic ATP Fuels the Plasma Membrane Calcium Pump Critical for Pancreatic Cancer Cell Survival
Investigators report that glycolytic inhibition induced profound ATP depletion, plasma membrane calcium pump inhibition, cytosolic Ca2+ overload and cell death in PANC1 and MIA PaCa-2 cells. [J Biol Chem] Abstract | Full Article

Loss of HAI-1 Participates in Metastatic Spreading of Human Pancreatic Cancer Cells in a Mouse Orthotopic Transplantation Model
To assess the significance of hepatocyte growth factor activator inhibitor type 1 (HAI-1) loss in invasion and spontaneous metastasis of S2-CP8 cells, scientists established stable S2-CP8 sublines that expressed HAI-1 under the control of a tetracycline-regulated promoter. In vitro migration and Matrigel invasion assays revealed inhibitory effects of HAI-1 on S2-CP8 cell migration and invasion. [Cancer Sci] Abstract

Upregulation of Wnt5a Promotes Epithelial-to-Mesenchymal Transition and Metastasis of Pancreatic Cancer Cells
The effects of Wnt5a overexpression or silencing on the invasiveness and epithelial-to-mesenchymal transition (EMT) of pancreatic cancer cells were studied. The percentage of Wnt5a positive expression showed a bell-shaped pattern in pancreatic cancer tissues, peaking in well-differentiated carcinomas. [BMC Cancer] Abstract | Full Article

Apigenin Potentiates the Growth Inhibitory Effects by Inhibitor of ?B Kinase-ß-Mediated NF-?B Activation in Pancreatic Cancer Cells
Scientists investigated the roles of nuclear factor-?B in apigenin-induced growth inhibition in pancreatic cancer cells. It showed that apigenin reduced cell growth and induced apoptosis in the cells. [Toxicol Lett] Abstract

PAF-Mediated MAPK Signaling Hyperactivation via LAMTOR3 Induces Pancreatic Tumorigenesis
Investigators identified a distinct function of PCNA-associated factor (PAF) in modulating mitogen-activated protein kinase (MAPK) signaling. PAF is overexpressed in pancreatic cancer and required for pancreatic cancer cell proliferation. [Cell Rep] Full Article | Graphical Abstract

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GABAergic System in ß-Cells: From Autoimmunity Target to Regeneration Tool
While the total function of ?-aminobutyric acid (GABA) in ß-cells is incompletely understood, its synthesizing enzyme glutamic acid decarboxylase is possibly one of the most significant pancreatic islet ß-cell autoantigens. [Diabetes] Abstract

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SWOG Initiates Randomized Phase II Clinical Trial of Halozyme’s PEGPH20 in Combination with Modified FOLFIRINOX for Advanced Pancreatic Cancer
Halozyme Therapeutics, Inc. announced the initiation of a Phase Ib/II randomized clinical trial of Halozyme’s investigational drug PEGPH20 (PEGylated Recombinant Human Hyaluronidase) in combination with modified FOLFIRINOX chemotherapy (mFOLFIRINOX) compared to mFOLFIRINOX treatment alone in patients with metastatic pancreatic adenocarcinoma. [Halozyme Therapeutics, Inc.] Press Release

BioLineRx Announces In-Licensing of BL-9020, for Treatment of Type 1 Diabetes
BioLineRx announced that it has signed a worldwide, exclusive license agreement with Yissum Research Development Company of the Hebrew University of Jerusalem, B.G. Negev Technologies and Applications Ltd., and Hadasit Medical Research Services and Development Ltd. for BioLineRx to develop and commercialize BL-9020, for the treatment of Type 1 diabetes. [BioLineRx] Press Release

Aduro Receives Orphan Drug Designation for CRS-207 for Pancreatic Cancer
Aduro BioTech, Inc. announced that the Office of Orphan Products Development of the Food and Drug Administration has granted orphan drug designation for CRS-207, a novel immunotherapy, for the treatment of pancreatic cancer. [Business Wire] Press Release

Harold Hamm Diabetes Center at The University of Oklahoma Awards First International Research Prize in Diabetes
Imagine how different the lives of so many would be if diabetes were cured and the billions of dollars in annual health care costs that could be saved. Finding that cure was the impetus for establishing the $250,000 Harold Hamm International Prize for Biomedical Research in Diabetes, awarded for the first time today by the Harold Hamm Diabetes Center at the University of Oklahoma. [PR Newswire Association LLC] Press Release

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NEW Keystone Symposia: Challenges and Opportunities in Diabetes Research and Treatment
January 12-17, 2014
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Visit our events page to see a complete list of events in the pancreatic cell community.
NEW Postdoctoral Associate Position – Molecular Mechanisms of Insulin Resistance and Beta-Cell Failure in Type 2 Diabetes (Nencki Institute of Experimental Biology)

Research Fellow – Cellular Immunity in Type 1 Diabetes (King’s College London)

Postdoctoral Position – Cell Metabolism, Diabetes and Fatty Liver Disease (Boston University)

Postdoctoral Associate – Human and Mouse Stem Cell Biology, Pancreatic and Liver Specification and In Vitro Disease Modeling (Baylor College of Medicine)

Postdoctoral Fellow – Molecular Mechanisms of Cancer Progression (University of South Alabama)

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

Faculty Position – Department of Cellular & Structural Biology (The University of Texas Health Science Center at San Antonio)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Research Associate – Particle Chemistry (STEMCELL Technologies Inc.)

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