Pancreatic Cell News Volume 4.27 | Jul 16 2013

Reconstituting Pancreas Development from Purified Progenitor Cells Reveals Genes Essential for Islet Differentiation
Researchers describe systems for reconstructing pancreas development, including islet ß-cell and a-cell differentiation, from single fetal progenitor cells. A strict requirement for native genetic regulators of in vivo pancreas development, such as Ngn3, Arx, and Pax4, revealed the authenticity of differentiation programs in vitro. [Proc Natl Acad Sci USA] Abstract

Biliary Tree Stem Cells, Precursors to Pancreatic Committed Progenitors: Evidence for Possible Life-Long Pancreatic Organogenesis
Researchers showed that proximal peribiliary glands-to-distal (PDGs) maturational lineages start near the duodenum with cells expressing markers of pluripotency, proliferation, self-replication, and early hepato-pancreatic commitment, transitioning to PDG cells with no expression of pluripotency or self-replication markers, maintenance of pancreatic genes, and expression of markers of pancreatic endocrine maturation. [Stem Cells] Abstract | Full Article

Identification of Particular Groups of MicroRNAs that Positively or Negatively Impact on Beta Cell Function in Obese Models of Type 2 Diabetes
The authors investigated the global changes in beta cell microRNA (miRNA) expression occurring in two models of obesity-associated type 2 diabetes and to assess their potential contribution to the development of the disease. MicroRNAs differentially expressed in both models of obesity-associated type 2 diabetes fall into two distinct categories. A group including miR-132, miR-184 and miR-338-3p displays expression changes occurring long before the onset of diabetes. [Diabetologia] Abstract

The Role of Thioredoxin 1 in the Mycophenolic Acid-Induced Apoptosis of Insulin-Producing Cells
To explore the effects of mycophenolic acid (MPA) and the relation between MPA and thioredoxin 1 (Trx-1), scientists used various methods, including an Illumina microarray, to identify the genes regulated during pancreatic ß-cell death following MPA treatment. INS-1E cells and isolated rat islets were treated with MPA for 12, 24, or 36 hours, and subsequent microarray analysis showed that gene expression was significantly reduced by MPA. [Cell Death Dis] Full Article

Multi-Parameter, Single-Cell, Kinetic Analysis Reveals Multiple Modes of Cell Death in Primary Pancreatic Beta-Cells
Scientists characterized the timing and order of molecular events associated with cell death in single ß-cells under multiple diabetic stress conditions, including hyperglycemia, cytokine exposure, nutrient deprivation and ER stress. They identified several cell death modes where the order of events that define apoptosis was not observed. [J Cell Sci] Abstract

Per-Arnt-Sim Kinase Regulates Pancreatic Duodenal Homeobox-1 Protein Stability via Phosphorylation of Glycogen Synthase Kinase 3 Beta in Pancreatic Beta Cells
The authors aimed to identify the role of Per-ARNT-Sim domain-containing kinase (PASK) in the regulation of pancreatic duodenal homeobox-1 (PDX-1) phosphorylation, protein expression and stability in insulin secreting cells and isolated rat islets of Langerhans. They observed that glucose induces a decrease in overall PDX-1 serine phosphorylation, and that overexpression of wild-type PASK mimics this effect. [J Biol Chem] Abstract | Full Article

PANCREATIC CANCER

Inactivating Mutations of RNF43 Confer Wnt Dependency in Pancreatic Ductal Adenocarcinoma
Researchers showed that ring finger 43 (RNF43) inhibits Wnt/ß-catenin signaling by reducing the membrane level of Frizzled in pancreatic cancer cells, serving as a negative feedback mechanism. Inhibition of endogenous Wnt/ß-catenin signaling increased the cell surface level of Frizzled. [Proc Natl Acad Sci USA] Abstract

Andrographolide Causes Apoptosis via Inactivation of STAT3 and Akt and Potentiates Antitumor Activity of Gemcitabine in Pancreatic Cancer
Scientists report that andrographolide (ANDRO) alone not only has anti-pancreatic cancer activity, but it also potentiates the anti-tumor activity of gemcitabine. Treatment with ANDRO alone inhibits proliferation of the pancreatic cancer cell lines in a dose- and time-dependent manner in vitro. [Toxicol Lett] Abstract

Pharmacodynamic Modeling of Cell Cycle and Apoptotic Effects of Gemcitabine on Pancreatic Adenocarcinoma Cells
To provide a quantitative framework for characterizing the cell cycle and apoptotic effects of gemcitabine, researchers developed a pharmacodynamic model in which the activation of cell cycle checkpoints or cell death is dependent on gemcitabine exposure. Model predictions and experimental data showed that gemcitabine induces cell cycle arrest in the S phase at low concentrations, whereas higher concentrations induce arrest in all cell cycle phases. [Cancer Chemother Pharmacol] Abstract

Cisplatin-Induced Non-Apoptotic Death of Pancreatic Cancer Cells Requires Mitochondrial Cyclophilin-D-p53 Signaling
Investigators found that cisplatin mainly induced non-apoptotic death of the pancreatic cancer cells, which was associated with a significant p53 activation. Further, activated p53 was found to translocate to mitochondria where it formed a complex with cyclophilin D. [Biochem Biophys Res Commun] Abstract

Current Understanding of the Molecular Biology of Pancreatic Neuroendocrine Tumors
Pancreatic neuroendocrine tumors are complicated and often deadly neoplasms. A recent increased understanding of their molecular biology has contributed to expanded treatment options. [J Natl Cancer Inst] Abstract

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ViaCyte, Inc. Raises $10.6 Million in a Private Financing to Support Clinical Development of Its Cell Therapy Product for Insulin Dependent Diabetes
ViaCyte, Inc., a regenerative medicine company focused on developing new approaches to treat major diseases through the application of a stem cell-derived cell therapy, announced that it completed a private equity financing transaction, providing the Company $10.6 million through the sale of Series C-1 Preferred Stock, together with warrants to purchase stock. [ViaCyte, Inc.] Press Release

Generex Oral-lyn™ Results in More Rapid Reductions of HbA1c in Shreya’s Phase III Study of Type 2 Diabetes in India
Generex Biotechnology Corporation announced the results of a Phase III clinical trial, conducted by its Indian licensee, Shreya Life Sciences Pvt. Ltd., of Generex Oral-lyn™, the Company’s proprietary buccal insulin spray product, in preparation for the approval for marketing and commercial distribution of the product in India, to be trademarked there as Oral Recosulin™. [Generex Biotechnology Corporation] Press Release

JDRF and Hundreds of Children Testify Before Senate on Need for Type 1 Diabetes Research Funding
JDRF’s president and CEO, Jeffrey Brewer, was joined by 2013 NBA champion Ray Allen of the Miami Heat, actress Jean Smart, and 150 children with type 1 diabetes (T1D) in a call for congressional support of T1D funding through legislation such as the Special Diabetes Program, which accounts for roughly one third of the federal investment in T1D research performed in the United States. [JDRF] Press Release

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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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