Pancreatic Cell News Volume 6.37 | Sep 22 2015

Inhibition of Hyaluronan Synthesis Restores Immune Tolerance during Autoimmune Insulitis
Researchers demonstrated that hyaluronan (HA) is critical for the pathogenesis of autoimmune diabetes. Using the DO11.10xRIPmOVA mouse model of type 1 diabetes, they determined that HA deposits are temporally and anatomically associated with the development of insulitis. [J Clin Invest] Full Article | Press Release

Isocitrate-to-SENP1 Signaling Amplifies Insulin Secretion and Rescues Dysfunctional β Cells
Investigators showed that the cytosolic isocitrate dehydrogenase-dependent generation of NADPH and subsequent glutathione reduction contribute to the amplification of insulin exocytosis via sentrin/SUMO-specific protease-1 (SENP1). [J Clin Invest] Full Article | Press Release

The mRNA-Binding Protein HuR Promotes Hypoxia-Induced Chemoresistance through Posttranscriptional Regulation of the Proto-Oncogene PIM1 in Pancreatic Cancer Cells
Investigators demonstrated that cis-acting AU-rich elements present within a 38-base pair region of the PIM1 (proviral integration site for moloney murine leukemia virus 1) mRNA 3′-untranslated region mediate a regulatory interaction with the mRNA stability factor HuR (Hu antigen R) in the context of tumor hypoxia. [Oncogene] Abstract

Autocrine Action of IGF2 Regulates Adult β Cell Mass and Function
Scientists studied mice with β cell-specific inactivation of Igf2 (βIGF2KO mice) and assessed β cell mass and function in ageing, pregnancy, and acute induction of insulin resistance. [Diabetes] Abstract

Induction of the ChREBPβ Isoform Is Essential for Glucose-Stimulated Beta Cell Proliferation
Researchers found that carbohydrate responsive element binding protein (ChREBP) is highly expressed in response to glucose, particularly with prolonged culture in hyperglycemic conditions. In addition, siRNAs that knocked down ChREBPβ transcripts without affecting ChREBPα expression or activity, decreased glucose-stimulated expression of ChoRE-containing genes and glucose-stimulated proliferation in INS-1 cells, and in isolated rat islets. [Diabetes] Abstract

The β-Cell GHSR and Downstream cAMP/TRPM2 Signaling Account for Insulinostatic and Glycemic Effects of Ghrelin
They authors report that ghrelin attenuates glucose-induced insulin release via direct interaction with ordinary growth hormone secretagogue-receptor (GHSR) that is uniquely coupled to novel cAMP/TRPM2 signaling in β-cells, and that this β-cell GHSR with unique insulinostatic signaling largely accounts for the systemic effects of ghrelin on circulating glucose and insulin levels. [Sci Rep] Full Article

Transient Receptor Potential Channel Vanilloid Type 6 (TRPV6)
Researchers characterized the role of TRPV6 in controlling calcium signaling, cell proliferation as well as insulin expression, and secretion in experimental INS-1E beta cell model. [Biochim Biophys Acta] Abstract

PANCREATIC CANCER

CD146 Attenuation in Cancer-Associated Fibroblasts Promotes Pancreatic Cancer Progression
Investigators clarified the function and significance of CD146 expression in pancreatic cancer. Blocking CD146 expression in cancer associated fibroblasts significantly enhanced tumor cell migration and invasion in a co-culture system. [Mol Carcinog] Abstract

Lysophosphatidic Acid Induces Both EGFR-Dependent and EGFR-Independent Effects on DNA Synthesis and Migration in Pancreatic and Colorectal Carcinoma Cells
Researchers investigated the effects of lysophosphatidic acid (LPA) on DNA synthesis and migration in a panel of pancreatic and colon cancer cells, with particular focus on the involvement of the epidermal growth factor receptor (EGFR) in LPA-induced signaling. [Tumor Biol] Abstract

Manganese Superoxide Dismutase Expression Is Negatively Associated with MicroRNA-301a in Human Pancreatic Ductal Adenocarcinoma
Researchers investigated whether the microRNA (miR)-301a expression level is associated with manganese superoxide dismutase (MnSOD) expression in human pancreatic ductal adenocarcinoma (PDAC). They established a xenograft PDAC mouse model using transfected PanC-1 cells to investigate tumor growth and the interaction between MnSOD and miR-301a. [Cancer Gene Ther] Abstract

Tetraspanin 1 Is Involved in Survival, Proliferation and Carcinogenesis of Pancreatic Cancer
Transfection with siRNA-targeting tetraspanin 1 (Tspan1) significantly decreased proliferation, increased the apoptosis and reduced migration and invasion of AsPC-1 and PANC-1 cells. [Oncol Rep] Abstract

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Caladrius Biosciences and Sanford Research Establish Strategic Collaboration with Goal of Developing Major Advance in Treatment of Type 1 Diabetes
Caladrius Biosciences, Inc. announced that it has entered into a collaboration agreement with Sanford Research to develop the company’s T regulatory cell therapy product candidate, CLBS03, for the treatment of adolescents with recent-onset type 1 diabetes. [Caladrius Biosciences, Inc.] Press Release

€3.3 Million Funding for DCU Transatlantic Pancreatic Cancer Research
Researchers at the University at Buffalo, Dublin City University (DCU) and Queen’s University Belfast have secured over €3.3 million to develop an enhanced treatment program for pancreatic cancer. [Dublin College University] Press Release

Groundbreaking Set for Additional Kimmel Cancer Center Building
The Johns Hopkins Kimmel Cancer Center broke ground September 10 on a new $100 million, 184,000-square-foot cancer care building. Slated to open in late 2017, the building is named for Albert P. “Skip” Viragh Jr., a Maryland mutual fund investment leader, philanthropist and pancreatic cancer patient treated at Johns Hopkins who died of the disease in 2003 at age 62. [Johns Hopkins Medicine] Press Release

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NEW Research Technician – Diabetes & Metabolism (University of Bristol)

Postdoctoral Fellowship – Action in Obesity and Diabetes Pathogenesis (National Institutes of Health Diabetes)

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Postdoctoral Position – Pancreatic Cancer (University of California, San Diego)

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Postdoctoral Position – Diabetes Research (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Research Fellow – Translational Research Program (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Scientist – Pancreatic Cancer (Columbia University)

Postdoctoral Research Fellow – Development and Pathogenesis of Pancreatic Cancer (University College London)

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