Volume 4.28 | Jul 23

Pancreatic Cell News 4.28 July 23, 2013
Pancreatic Cell News
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Loss of Prohibitin Induces Mitochondrial Damages Altering ß-Cell Function and Survival and Responsible for Gradual Diabetes Development
The authors document the expression of prohibitins in human and rodent islets, and their key role for ß-cell function and survival. Ablation of Phb2 in mouse ß-cells sequentially resulted in impairment of mitochondrial function and insulin secretion, loss of ß-cells, progressive alteration of glucose homeostasis, and ultimately severe diabetes. [Diabetes] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

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


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

Differentiation Doesn't Have to be Difficult Get Easy, Standardized hPSC Differentiation
The Use of Stem Cells for Pancreatic Regeneration in Diabetes Mellitus
One of the major pancreatic diseases, diabetes mellitus is a metabolic disorder caused by having an insufficient number of insulin-producing ß cells. Replenishment of ß cells by cell transplantation can restore normal metabolic control. The shortage in donor pancreata has meant that the demand for transplantable ß cells has outstripped the supply, which could be met by using alternative sources of stem cells. This situation has opened up new areas of research, such as cellular reprogramming and in vivo ß-cell regeneration. [Nat Rev Endocrinol] 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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Boehringer Ingelheim and EFSD Announce First Recipients of Diabetes Research Funding
The Boehringer Ingelheim and European Foundation for the Study of Diabetes (EFSD) partnership announced the recipients of their European-wide funding initiative targeted at diabetes research. Totaling €2.5 million, these are the first grants to be awarded as part of the EFSD/Boehringer Ingelheim European Diabetes Research Programs, which aim to stimulate and accelerate European research in diabetes. [Boehringer Ingelheim GmbH] Press Release

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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NEW Joint Meeting of International Association of Pancreatology (IAP) and Korean Pancreatobiliary Association (KPBA) 2013
September 4-7, 2013
Seoul, Korea

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NEW Postdoctoral Fellow – Diabetes Research (Sanford Health)

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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