Pancreatic Cell News Volume 3.37 | Sep 18 2012

DIABETES

MicroRNAs Contribute to Compensatory β Cell Expansion during Pregnancy and Obesity
Researchers found in rodents that β cell mass expansion during pregnancy and obesity is associated with changes in the expression of several islet microRNAs (miRNAs), including miR-338-3p. In isolated pancreatic islets, they recapitulated the decreased miR-338-3p level observed in gestation and obesity by activating the G protein-coupled estrogen receptor GPR30 and the glucagon-like peptide 1 receptor. [J Clin Invest]
Full Article

A Local Glucagon-Like Peptide 1 (GLP-1) System in Human Pancreatic Islets
Scientists evaluated the presence and various features of a local GLP-1 system in human pancreatic islet cells, including those from type 2 diabetic patients. [Diabetologia] Abstract

B7x in the Periphery Abrogates Pancreas-Specific Damage Mediated by Self-Reactive CD8 T Cells
Investigators showed that B7x protein was not detected on APCs or T cells in both human and mice, which is unique in the B7 family. Because B7x protein is expressed in some peripheral cells such as pancreatic β cells, a CD8 T cell-mediated diabetes model (AI4αβ) was used in which CD8 T cells recognized an endogenous self-Ag, and found that mice lacking B7x developed more severe diabetes than control AI4αβ mice. [J Immunol] Abstract

Vitamin D Receptor Activation Induces Peptide YY Transcription in Pancreatic Islets
Researchers investigated the role of pancreatic vitamin D receptor (VDR) activation and found that Peptide YY (Pyy) is a VDR target gene in the mouse pancreas. VDR activation increased mRNA and protein expression of PYY in the pancreatic islets of mice and pancreatic endocrine cell lines but did not change intestinal PYY expression. [Endocrinology] Abstract

Re-Expression of IGF-II Is Important for Beta Cell Regeneration in Adult Mice
Scientists investigated the effect of insulin-like growth factor II (IGF-II) on beta cell regeneration. They employed an in vivo model of c-Myc-induced beta cell ablation, pIns-c-MycER^TAM. IGF-II was shown to be re-expressed in the adult pancreas of pIns-c-MycER^TAM/IGF-II^+/+ mice, following beta cell injury. [PLoS One]
Full Article

PANCREATIC CANCER

Endoneurial Macrophages Induce Perineural Invasion of Pancreatic Cancer Cells by Secretion of Glial-Derived Neurotrophic Factor and Activation of RET Tyrosine Kinase Receptor
Immunohistochemical analysis of specimens excised from patients with pancreatic adenocarcinomas (PDAs) showed a significant increase in the number of endoneurial macrophages (EMΦs) which lie around nerves invaded by cancer compared to normal nerves. Conditioned medium of tumor-activated EMΦs induced a five-fold increase in migration of PDA cells compared to controls. [Cancer Res] Abstract

Overexpression of Ecdysoneless (Ecd) in Pancreatic Cancer and Its Role in Oncogenesis by Regulating Glycolysis
Researchers studied the expression and function of a novel cell cycle regulatory protein, human ecdysoneless, during pancreatic cancer (PC) pathogenesis. To analyze the biological significance of Ecd in PC progression, Ecd was stably knocked down in PC cell line followed by in vitro and in vivo functional assays. [Clin Cancer Res] Abstract

REG4 Contributes to the Invasiveness of Pancreatic Cancer by Upregulating MMP-7 and MMP-9
Scientists explored the role of regenerating gene family member 4 (REG4) in the invasion of pancreatic cancer. Two MMPs (matrix metalloproteinase), MMP-7 and MMP-9, were identified from a pool of candidate genes to be related to REG4 induced cell invasion by real-time reverse transcription-polymerase chain reaction and western blotting. [Cancer Sci] Abstract

Cancer Specific Promoter CpG Islands Hypermethylation of Homeodomain Only Protein X Gene and Its Potential Tumor Suppressive Role in Pancreatic Carcinogenesis
Investigators examined methylation level of homeodomain only protein X (HOPX) and tested the functional relevance in pancreatic cancer (PC). Clinical features of HOPX promoter hypermethylation were investigated in PC tissues, and immunohistochemistry was added. They also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis. [BMC Cancer]
Abstract | Full Article

Knockdown of Clusterin Sensitizes Pancreatic Cancer Cells to Gemcitabine Chemotherapy by ERK1/2 Inactivation
Researchers investigated whether gemcitabine treatment augments the chemoresistance to gemcitabine by clusterin upregulation. Clusterin inhibition could augment the chemosensitivity of human pancreatic cancer cells by inhibition of clusterin-dependent pERK1/2 activation. [J Exp Clin Cancer Res] Abstract | Full Article

REVIEWS

Zealand Pharma Advances ZP2929 into Phase I Development for the Treatment of Type 2 Diabetes and/or Obesity
Zealand Pharma A/S announced that the first participant has been dosed in the first phase I clinical study of ZP2929. ZP2929 is a dual acting glucagon/GLP-1 peptide agonists for the treatment of patients with type 2 diabetes and/or patients with obesity. [Zealand Pharma A/S] Press Release

Beta Cells in 3D
Juvenile Diabetes Research Foundation- funded researchers at the Technion Israel Institute of Technology have built pancreatic tissue surrounded by a 3D network of blood vessels. When beta cells were grown in the same surroundings as they would have in the body, they survived for longer. [Juvenile Diabetes Research Foundation Ltd] Press Release

Islet Sciences Names Richard A. Franco, Sr. to Its Board of Directors
Islet Sciences, Inc., a biotechnology company engaged in the research, development and commercialization of patented technologies in the field of transplantation therapy for patients with diabetes announced that the company has named Richard A. Franco, Sr. to its Board of Directors. [Islet Sciences, Inc.] Press Release

Sequestration Would Cut U.S. Science Budgets by 8.2%, White House Estimates
U.S. government science funding programs would see their budgets cut by 8.2% in 2013 unless Congress agrees on a plan to trim budget deficits by the start of the new year. [White House, United States]
Press Release

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European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW 9^th Stem Cell Research & Therapeutics Conference
October 24-26, 2012
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Clinical Investigator – Biomedical Research Program (Weill Cornell Medical College)

Postdoctoral Position – Type 2 Diabetic Human Induced Pluripotent Stem Modeling (University of Lille Nord de France)

Postdoctoral Position – Cancer Therapeutics (Massachusetts General Hospital)

Postdoctoral Position – Dysfunction in Diabetes (University of Oxford)

Postdoctoral Position – Beta Cell Biology and Translational Research (University of California, Los Angeles)

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

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