Pancreatic Cell News Volume 3.43 | Oct 30 2012

DIABETES

Modification of Ghrelin Receptor Signaling by Somatostatin Receptor-5 Regulates Insulin Release
The data presented are consistent with physiologically relevant noncanonical ghrelin receptor:somatostatin (SST) receptor subtype 5 heteromerization that explains differential regulation of islet function by ghrelin and SST. These findings reinforce the concept that signaling by the G-protein receptor is dynamic and dependent on protomer interactions and physiological context. [Proc Natl Acad Sci USA] Abstract

Ectopic Expression of GIP in Pancreatic β-Cells Maintains Enhanced Insulin Secretion in Mice with Complete Absence of Proglucagon-Derived Peptides
Results indicated that ectopic glucose-dependent insulinotropic polypeptide (GIP) expression in β-cells maintains insulin secretion in the absence of proglucagon-derived peptides, revealing a novel compensatory mechanism for sustaining incretin hormone action in islets. [Diabetes] Abstract

Nonviral-Mediated Hepatic Expression of IGF-I Increases Regulatory T-Cell Levels and Suppresses Autoimmune Diabetes in Mice
Researchers demonstrated that transient, plasmid-derived IGF-I expression in mouse liver suppressed autoimmune diabetes progression. Suppression was associated with decreased islet inflammation and β-cell apoptosis, increased β-cell replication, and normalized β-cell mass. [Diabetes] Abstract

Human Blood Outgrowth Endothelial Cells Improve Islet Survival and Function When Co-Transplanted in a Mouse Model of Diabetes
The authors evaluated a potentially beneficial effect of adult human blood outgrowth endothelial cells on islet graft vascularization and function. [Diabetologia] Abstract

Contribution of 24 Obesity-Associated Genetic Variants to Insulin Resistance, Pancreatic Beta-Cell Function and Type 2 Diabetes Risk in the French Population
Investigators aimed at analyzing the effect of 24 obesity risk alleles, separately and in combination, on variation of both insulin resistance and β-cell dysfunction, and on type 2 diabetes risk. [Int J Obesity] Abstract

PANCREATIC CANCER

Effects of Oxidative Alcohol Metabolism on the Mitochondrial Permeability Transition Pore and Necrosis in a Mouse Model of Alcoholic Pancreatitis
Scientists investigated the effects of ethanol on the pancreatic mitochondrial permeability transition pore, the mechanisms of these effects, and their role in pancreatitis. [Gastroenterology] Abstract

Inhibition of the Nrf2 Transcription Factor by the Alkaloid Trigonelline Renders Pancreatic Cancer Cells More Susceptible to Apoptosis through Decreased Proteasomal Gene Expression and Proteasome Activity
Pancreatic carcinoma cell lines and H6c7 pancreatic duct cells were analyzed for the nuclear factor E2-related factor 2 (Nrf2)-inhibitory effect of the coffee alkaloid trigonelline, as well as for its impact on Nrf2-dependent proteasome activity and resistance to tumor necrosis factor-related apoptosis-inducing ligand and anticancer drug-induced apoptosis. [Oncogene] Abstract

MUC1 Enhances Hypoxia-Driven Angiogenesis through the Regulation of Multiple Proangiogenic Factors
Using the conditioned medium obtained from hypoxia-stressed AsPC1 cells treated with mucin 1 (MUC1) siRNAs, scientists demonstrated that MUC1 enhanced the endothelial tube formation, proliferation and migration ability, which induced by hypoxia-conditioned medium. In addition, MUC1 was significantly induced by hypoxia, especially in the pancreatic cancer cells derived from metastatic tumors, and MUC1-cytoplasmic tail accumulated in the nucleus under hypoxia. [Oncogene] Abstract

Exosomal Lipids Impact Notch Signaling and Induce Death of Human Pancreatic Tumoral SOJ-6 Cells
Researchers previously reported that exosomes secreted by human SOJ-6 pancreatic tumor cells induce (glyco)protein ligand-independent cell death and inhibit Notch-1 pathway, this latter being particularly active during carcinogenesis and in cancer stem cells. Therefore, they evaluated whether exosomal lipids were key-elements for cell death and hypothesized that cholesterol-rich membrane microdomains were privileged sites of exosome interactions with tumor cells. [PLoS One] Full Article

Gene Therapy of Pancreatic Cancer Targeting the K-Ras Oncogene
Ras mutations are present in ~95% of pancreatic cancer cases leading to increased proliferation and apoptosis resistance. The aim of this study was to selectively kill Ras-transformed cells by overexpressing the pro-apoptotic protein, p53 upregulated modulator of apoptosis under a Ras-responsive promoter. [Cancer Gene Ther] Abstract

REVIEWS

ViaCyte Receives $10.1 Million Strategic Partnership Award from CIRM to Continue Development of Diabetes Therapy
ViaCyte, Inc. announced that it has received a $10.1 million Strategic Partnership Award from the California Institute for Regenerative Medicine (CIRM). ViaCyte’s innovative stem cell-based therapy for diabetes has been supported by several previous rounds of funding from CIRM, including a $20 million Disease Team Award in 2009. [ViaCyte, Inc.] Press Release

Type 1 Diabetes (T1D): Enrollment of the First Patient Kicks off International Phase III Trial on Reparixin, the Investigational Drug Developed by Dompé R&D
Dompé announced the enrollment of the first patient into a Phase III trial on Reparixin, the compound that has shown to improve the efficacy of transplantation of insulin-producing pancreatic islets, which is the new frontier in T1D treatment. [Business Wire] Press Release

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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)

Quality Control Operations Coordinator (STEMCELL Technologies, Inc.)

Research Technologist – Cell Separation (STEMCELL Technologies, Inc.)

Product Manager – Hematopoietic (STEMCELL Technologies, Inc.)

Product Quality Scientist (STEMCELL Technologies, Inc.)

Scientist – Endothelial Cell Research (STEMCELL Technologies, Inc.)

Scientific Communications & Publishing Coordinator (STEMCELL Technologies, Inc.)

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

Postdoctoral Position – Signaling Pathways Pancreatic Beta-Cells (CNRS – Centre National de la Recherche Scientifique)

Postdoctoral Position – Beta Cell Biology (Umea Center for Molecular Medicine)

Postdoctoral Position – Tumor Stem Cells (Cancer Institute of New Jersey)

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