Pancreatic Cell News Volume 7.06 | Feb 16 2016

Haplo-Insufficiency of the Insulin Receptor in the Presence of a Splice-Site Mutation in Ppp2r2a Results in a Novel Di-Genic Mouse Model of Type 2 Diabetes
Researchers present a novel digenic model of type 2 diabetes in mice heterozygous for a null allele of the Insulin Receptor and an N-ethyl-N-nitrosourea induced alternative splice mutation in the regulatory protein phosphatase 2A (PP2A) subunit Ppp2r2a. [Diabetes] Abstract

IP Receptor Agonism Preserves Beta-Cell Function and Attenuates Albuminuria through Nephrin-Dependent Mechanisms
Scientists investigated the in vitro and in vivo effects of pharmacological agonism of the prostaglandin I2 (IP) receptor in pancreatic ß-cells and in glomerular podocytes. The IP receptor agonist MRE-269 increased intracellular cAMP, augmented glucose-stimulated insulin secretion (GSIS) and increased viability in MIN6 ß-cells and its pro-drug form, selexipag augmented GSIS and preserved islet ß-cell mass in diabetic mice. [Diabetes] Abstract

Pancreatic β-Cell Membrane Fluidity and Toxicity Induced by Human Islet Amyloid Polypeptide Species
Researchers showed a biophysical scheme based on the use of a lipophilic Laurdan dye for examining MIN6 cell membranes upon exposure to fresh and oligomeric hIAPP as well as mature amyloid. [Sci Rep] Full Article

Cyclin-Dependent Kinase 2 Protects Podocytes from Apoptosis
Investigators found that treatment of podocytes with sera from normoalbuminuric type 1 diabetes patients with high lipopolysaccharide (LPS) activity, known to predict progression of diabetic nephropathy, downregulated cyclin-dependent kinase 2 (CDK2). LPS-treatment of mice also reduced CDK2 expression. [Sci Rep] Full Article

Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia
The authors differentiated HNF1B^S148L/+ mutation (MODY5) human-induced pluripotent stem cells (hiPSCs) into pancreatic progenitors, and showed that the HNF1B^S148L/+ mutation causes a compensatory increase in several pancreatic transcription factors, and surprisingly, a decrease in PAX6 pancreatic gene expression. [Stem Cell Reports] Full Article | Graphical Abstract

PANCREATIC CANCER

AAVP Displaying Octreotide for Ligand-Directed Therapeutic Transgene Delivery in Neuroendocrine Tumors of the Pancreas
Investigators designed a hybrid adeno-associated virus and phage (AAVP) vector displaying biologically active octreotide on the viral surface for ligand-directed delivery, cell internalization, and transduction of an apoptosis-promoting tumor necrosis factor transgene specifically to pancreatic neuroendocrine tumors. [Proc Natl Acad Sci USA] Full Article | Abstract

Extracellular Lumican Augments Cytotoxicity of Chemotherapy in Pancreatic Ductal Adenocarcinoma Cells via Autophagy Inhibition
Scientists investigated the role of extracellular lumican in chemotherapy-mediated cancer therapy. Lumican secretion was increased by chemotherapeutic agents in pancreatic ductal adenocarcinoma cells, and especially in pancreatic stellate cells, and appeared to be linked to the extent of cells’ response to chemotherapy-induced growth inhibition. [Oncogene] Abstract

HGF/Met and FOXM1 Form a Positive Feedback Loop and Render Pancreatic Cancer Cells Resistance to Met Inhibition and Aggressive Phenotypes
The mechanistic role of cross talk between Forkhead box M1 (FOXM1) and hepatocyte growth factor (HGF)/Met signaling in promotion of pancreatic ductal adenocarcinoma (PDA) growth and resistance to Met inhibition was examined using cell culture, molecular biology and mouse models; and the relevance of the investigators’ experimental and mechanistic findings were validated using human PDA tissues. [Oncogene] Abstract

The E1B19K-Deleted Oncolytic Adenovirus Mutant AdΔ19K Sensitizes Pancreatic Cancer Cells to Drug-Induced DNA-Damage by Down-Regulating Claspin and Mre11
Researchers found that adenovirus prevents Chk1-mediated checkpoint activation through inactivation of Mre11 and downregulation of the pChk1 adaptor-protein, Claspin, in cells with high levels of DNA-damage induced by the cytotoxic drugs gemcitabine and irinotecan. [Oncotarget] Full Article

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JDRF Announces the Formation of a New Research Advisory Committee to Support Fight against Type 1 Diabetes
JDRF, the leading global organization funding type 1 diabetes (T1D) research, announced the formation of a new external Research Advisory Committee comprised of individuals internationally renowned for their expertise in research as well as the care and treatment of those with T1D. [JDRF (PR Newswire Association LLC)] Press Release

Incyte Announces Decision to Discontinue JANUS Studies of Ruxolitinib plus Capecitabine in Patients with Advanced or Metastatic Pancreatic Cancer
Incyte Corporation announced its decision to discontinue the Phase III study (JANUS 1) of ruxolitinib or placebo in combination with capecitabine for the second-line treatment of patients with advanced or metastatic pancreatic cancer. The decision to stop the study was made after a planned interim analysis of JANUS 1 demonstrated that ruxolitinib plus capecitabine did not show a sufficient level of efficacy to warrant continuation. [Incyte Corporation] Press Release

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NEW Postdoctoral Fellowship – Neural Mechanisms of Diabetes (Albert Einstein College of Medicine)

NEW Postdoctoral Fellowship – Atherosclerosis and Diabetes (Virginia Commonwealth University)

Faculty Position – Metabolic Disease Research (Lewis Katz School of Medicine)

Postdoctoral Fellowship – Diabetes (Danish Diabetes Academy)

Post-Doc Fellowship – Glucose Metabolism (Joslin Diabetes Center)

Post-Doc Researcher – Drug Discovery in Cancer/Diabetes (D. E. Shaw Research)

Post-Doc Fellowship – Diabetes Research (Sanford Research/University of South Dakota)

Faculty Position – Biomedical Metabolomics & Metabolism (University of Ottawa)

Visiting Scientist – Diabetes (Danish Diabetes Academy)

Post-Doc Researcher – Type 1 Diabetes (University of Turku)

MD/PhD Researcher – Biomedical Sciences (Hannover Medical School)

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