Pancreatic Cell News Volume 4.08 | Mar 5 2013

DIABETES

Identification of a SIRT1 Mutation in a Family with Type 1 Diabetes
Scientists describe a family carrying a mutation in the SIRT1 gene, in which all five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis. Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107 (SIRT1-L107P). Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines. [Cell Metab] Abstract | Press Release

Munc18b Is a Major Mediator of Insulin Exocytosis in Rat Pancreatic β-Cells
Scientists found that Munc18b depletion in rat islets disabled SNARE complex formation formed by Syntaxin-2 and Syntaxin-3. Two-photon imaging analysis revealed in Munc18b-depleted β-cells a 40% reduction in primary exocytosis and abrogation of almost all sequential secretory granule (SG)-SG fusion, together accounting for a 50% reduction in glucose-stimulated insulin secretion. [Diabetes] Abstract

Stromal Cell-Derived Factor 2 Like-1 (SDF2L1) Associates with the Endoplasmic Reticulum-Associated Degradation (ERAD) Machinery and Retards the Degradation of Mutant Proinsulin in Pancreatic β-Cells
Researchers showed that SDF2L1 protein levels are increased in response to endoplasmic reticulum stress-inducing compounds, but not other cell stressors they tested in insulinoma cell lines. SDF2L1 protein levels were also induced by expression of misfolded proinsulin in insulinoma cells and in islets from diabetic mice. [J Cell Sci] Abstract

The Hydrolase DDAH2 Enhances Pancreatic Insulin Secretion by Transcriptional Regulation of Secretagogin through a Sirt1-Dependent Mechanism in Mice
The authors generated dimethylarginine dimethylaminohydrolase 2 (DDAH2) transgenic (Tg) mice that had lower plasma glucose levels and higher insulin levels during intraperitoneal glucose tolerance tests when fed a high-fat diet (HFD) compared with HFD-fed wild-type mice. Glucose-stimulated insulin secretion was increased in Tg islets by 33%. [FASEB J] Abstract

PANCREATIC CANCER

Hippo Signaling Regulates Differentiation and Maintenance in the Exocrine Pancreas
Researchers investigated the role of the core Hippo kinases-Mst1 and Mst2-in pancreatic development and homeostasis. They used a Cre/LoxP system to create mice with pancreas-specific disruptions in Mst1 and Mst2, the mammalian orthologs of Drosophila Hippo. [Gastroenterology] Abstract

PARI Overexpression Promotes Genomic Instability and Pancreatic Tumorigenesis
The authors showed that an element of the homologous recombination pathway of DNA repair, the PARP-binding protein C12orf48/PARI, is overexpressed specifically in pancreatic cancer cells where it is an appealing candidate for targeted therapy. PARI upregulation in pancreatic cancer cells or avian DT40 cells conferred DNA repair deficiency and genomic instability. [Cancer Res] Abstract

Aberrant Expression of Mucin Core Proteins and O-Linked Glycans Associated with Progression of Pancreatic Cancer
Scientists investigated the expression of a number of mucin core proteins and associated O-linked glycans expressed in pancreatic adenocarcinoma – sialyl Tn, Tn, T antigen, sialyl Lewis A, sialyl Lewis C, Lewis X and sialyl Lewis X – during the progression of pancreatic cancer from early stages to metastatic disease. [Clin Cancer Res] Abstract

Suppression of AKT Phosphorylation Restores Rapamycin-Based Synthetic Lethality in SMAD4-Defective Pancreatic Cancer Cells
Researchers report that SMAD4-deficient pancreatic cancer cells are killed by rapamycin in the absence of serum; however, in the presence of serum they did not observe the predicted synthetic lethality with rapamycin. Rapamycin also induced elevated phosphorylation of the survival kinase Akt at Ser473. Suppression of rapamycin-induced Akt phosphorylation restored rapamycin sensitivity in SMAD4 null, but not SMAD4 wild type pancreatic cancer cells. [Mol Cancer Res] Abstract

Net Expression Inhibits the Growth of Pancreatic Ductal Adenocarcinoma Cell PL45 In Vitro and In Vivo
Using in vitro and in vivo model systems, researchers found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. [PLoS One] Full Article

REVIEWS

Diabetes Research Institute Tests BioHub Mini Organ to Restore Natural Insulin Production in Type 1 Diabetes
Scientists from the Diabetes Research Institute (DRI) at the University of Miami are taking a quantum leap toward a biological cure for diabetes by unveiling the DRI BioHub, a bioengineered “mini organ” that contains lifesaving insulin-producing cells that can sense blood sugar and release the precise amount of insulin needed in real time. [Diabetes Research Institute Foundation] Press Release

CeQur Announces Positive Results from Study Evaluating Simple Insulin Delivery Device Among People with Type 2 Diabetes
CeQur SA announced initial data from a study of the company’s PaQ^® Insulin Delivery Device. The data suggest that PaQ is a safe, highly satisfying alternative to multiple daily insulin injections for people with type 2 diabetes – many of whom need new tools to help them achieve better glycemic control. [CeQur LTD] Press Release

State Food and Drug Administration Grants Approval to Sihuan Pharmaceutical for Clinical Trial of Innovative Drug – Pinoxacin Hydrochloride
Sihuan Pharmaceutical Holdings Group Ltd. announced that Pinoxacin Hydrochloride received Approval for Clinical Studies from the State Food and Drug Administration. Phase I of clinical studies are set to begin in the first half of this year. Pinoxacin Hydrochloride is DPP-4 inhibitor class of oral hypoglycemic agents, a drug with a brand new structure for treating type II diabetes. [PR Newswire Association LLC] Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)
 
Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

National Health Service (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW Cold Spring Harbor Laboratory: Workshop on Pancreatic Cancer
June 26- July 2, 2013
Cold Spring Harbor, United States

Visit our events page to see a complete list of events in the pancreatic cell community.

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

Postdoctoral Position – Pancreatic Beta-Cell Dysfunction (Weill Cornell Medical College)

Postdoctoral Position – Pancreas Development (INSERM)

PhD Studentship – Developmental Genes in Adult Pancreas Homeostasis & Energy Metabolism (Helmholtz Zentrum München)

Research Position – Diabetes Research (Johns Hopkins University)

Senior Scientist (Spiber Technologies AB)

Postdoctoral Position – Basic Diabetes Research (Université Libre de Bruxelles)

Postdoctoral Position – Mechano-Signaling in the Regulation of Pancreatic Cancer Progression (Fox Chase Cancer Center)

Postdoctoral Position – Compensatory Beta-Cell Proliferation (Karolinska Institutet)

Postdoctoral Position (New York University)

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