Pancreatic Cell News Volume 4.28 | Jul 23 2013

ß1 Integrin Is a Crucial Regulator of Pancreatic ß-Cell Expansion
Researchers showed that ablation of the ß1 integrin gene in developing pancreatic ß-cells reduces their ability to expand during embryonic life, during the first week of postnatal life, and thereafter. Mice lacking ß1 integrin in insulin-producing cells exhibit a dramatic reduction of the number of ß-cells to only ~18% of wild-type levels. [Development] Abstract

Neurogenin3 Activation Is not Sufficient to Direct Duct-to-Beta Cell Transdifferentiation in the Adult Pancreas
Researchers studied two models of neurogenin3 (Ngn3) activation in adult pancreatic duct cells and lineage-traced Ngn3-activated duct cells by labeling them through intraductal infusion with a cell-tagging dye, CFDA-SE. No dye-labeled beta cells were found during the follow-up in either model, suggesting that activation of Ngn3 in duct cells is not sufficient to direct their transdifferentiation into beta cells. [J Biol Chem]
Abstract | Full Article

Insulin Receptor-Overexpressing ß-Cells Ameliorate Hyperglycemia in Diabetic Rats through Wnt Signaling Activation
To investigate the therapeutic efficacy and mechanism of ß-cells with insulin receptor overexpression on diabetes mellitus, rat insulinoma (INS-1) cells were engineered to stably express human insulin receptor (INS-IR cells), and subsequently transplanted into streptozotocin- induced diabetic rats. Compared with INS-1 cells, INS-IR cells showed improved ß-cell function, including the increase in glucose utilization, calcium mobilization, and insulin secretion, and exhibited a higher rate of cell proliferation, and maintained lower levels of blood glucose in diabetic rats. [PLoS One] Full Article

Grape Seed Proanthocyanidins Ameliorate Pancreatic Beta-Cell Dysfunction and Death in Low-Dose Streptozotocin- and High-Carbohydrate/High-Fat Diet-Induced Diabetic Rats Partially by Regulating Endoplasmic Reticulum Stress
Researchers investigated the effect of grape seed proanthocyanidins (GSPs) on beta-cell failure and endoplasmic reticulum (ER) stress in diabetic pancreas. GSPs treatment increased normal insulin content and decreased the number of apoptotic cells in diabetic islets. [Nutr Metab] Abstract | Full Article

PANCREATIC CANCER

Lamin B1 Is a Novel Therapeutic Target of Betulinic Acid in Pancreatic Cancer
Scientists determined the role and regulation of lamin B1 expression in human pancreatic cancer pathogenesis and betulinic acid (BA)-based therapy. They found that lamin B1 was significantly downregulated by BA treatment in pancreatic cancer in both in vitro culture and xenograft models. [Clin Cancer Res] Abstract

A Novel Epigenetic CREB-miR-373 Axis Mediates ZIP4-Induced Pancreatic Cancer Growth
Researchers report a novel mechanism where increased zinc mediated by the zinc importer ZIP4 transcriptionally induces microRNA (miR)-373 in pancreatic cancer to promote tumor growth. [EMBO Mol Med] Abstract | Full Article

Reolysin Is a Novel Reovirus-Based Agent that Induces Endoplasmic Reticular Stress-Mediated Apoptosis in Pancreatic Cancer
Scientists report that Reolysin treatment stimulated selective reovirus replication and decreased cell viability in KRas-transformed immortalized human pancreatic duct epithelial cells and pancreatic cancer cell lines. These effects were associated with increased expression of endoplasmic reticular (ER) stress-related genes, ER swelling, cleavage of caspase-4, and splicing of XBP-1. [Cell Death Dis] Full Article

Multifunctional Roles of Urokinase Plasminogen Activator (uPA) in Cancer Stemness and in Chemo-Resistance of Pancreatic Cancer
Scientists examined the role of uPA in the generation of pancreatic ductal adenocarcinoma-cancer stem cells (CSC). They observed a subset of cells identifiable as a side-population when sorted by flow-cytrometry of MIA PaCa-2 and PANC-1 pancreatic cancer cells that possessed the properties of CSC. [Mol Biol Cell] Abstract

The CX3CL1/CX3CR1 Reprograms Glucose Metabolism through HIF-1 Pathway in Pancreatic Adenocarcinoma
Investigators found that CX3CR1 is expressed in pancreatic cancer cells lines. Exogenous or transfected CX3CL1 increased glucose uptake and lactate secretion. CX3CL1 stimulated HIF-1 expression through PI3K/Akt and MAPK pathways. [J Cell Biochem] Abstract

Mucins in Pancreatic Cancer and Its Microenvironment
The authors discuss the expression pattern of various mucins in the pancreas under healthy, inflammatory, and cancerous conditions; the context-dependent attributes of mucins that differ under healthy and pathological conditions; the contribution of the tumor microenvironment in pancreatic cancer development and/or progression; diagnostic and/or prognostic efficacy of mucins; and mucin-based therapeutic strategies. [Nat Rev Gastroenterol Hepatol] Abstract

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NGM Biopharmaceuticals Secures $50 Million in Series C Financing to Advance Its Portfolio of Novel Therapies for Diabetes and Obesity
NGM Biopharmaceuticals, Inc. announced the successful completion of a $50 million Series C financing to support advancing its portfolio of potential therapeutics for the treatment of diabetes, obesity and other cardio-metabolic diseases. [NGM Biopharmaceuticals, Inc.] Press Release

Perrigo Receives FDA Tentative Approval for Generic Equivalent to Prandin^®
Perrigo Company announced that it has received tentative approval from the U.S. Food & Drug Administration (FDA) for its abbreviated new drug application for repaglinide tablets, the generic equivalent to Prandin^® Tablets. Prandin^® tablets, are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes mellitus. [Perrigo Company] Press Release

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Postdoctoral Researcher – Molecular Determinants of Resistance to Chemotherapy and Radiation (The Ohio State University – Comprehensive Cancer Center)

Postdoctoral Electrophysiologist (University of Alberta)

Postdoctoral Position – Pluripotent Stem Cells to Islets (INSERM)

Postdoctoral Research Fellow – Platelet Biology and Diabetes (Thomas Jefferson University, Cardeza Foundation for Hematologic Research)

Director of Cell Processing Facility (S L Collins Associates, Inc.)

Diabetes UK PhD Studentship (Diabetes UK)

PhD Positions – Molecular Mechanisms Controlling Acinar Cell Proliferation (University Hospital Zuerich)

Postdoctoral Researcher (The University of Texas Health Science Center at San Antonio)

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