Pancreatic Cell News Volume 6.24 | Jun 23 2015

DNA Methylation Directs Functional Maturation of Pancreatic β Cells
DNA methyltransferase (DNMT3A) bound to the promoters of the genes encoding hexokinase 1 and lactate dehydrogenase A—both of which regulate the metabolic switch—and knockdown of these two key DNMT3A targets restored the glucose-stimulated insulin secretion response in islets from animals with β cell-specific Dnmt3a deletion. [J Clin Invest] Full Article

Islet Amyloid Inhibitors Improve Glucose Homeostasis in a Transgenic Mouse Model of Type 2 Diabetes
To assess its activity in vivo, D-ANFLVH was administered by intraperitoneal injection into a human islet amyloid polypeptide transgenic mouse model, which replicates type 2 diabetes islet amyloid pathology. The peptide was a potent inhibitor of islet amyloid deposition, resulting in reduced islet cell apoptosis and preservation of beta cell area leading to improved glucose tolerance. [Diabetes Obes Metab] Abstract

Nitric Oxide Stress and Activation of AMP-Activated Protein Kinase Impair β-Cell Sarcoendoplasmic Reticulum Calcium ATPase 2b Activity and Protein Stability
Investigators previously demonstrated loss of β-cell sarcoendoplasmic reticulum Ca²⁺ ATPase 2b expression under diabetic conditions. To define the mechanisms underlying this, INS-1 cells and rat islets were treated with the proinflammatory cytokine interleukin-1β combined with or without cycloheximide or actinomycin D. [Cell Death Dis] Full Article

Regulation of Pancreatic β Cell Mass by Cross-Interaction between CCAAT Enhancer Binding Protein β Induced by Endoplasmic Reticulum Stress and AMP-Activated Protein Kinase Activity
Scientists aimed to elucidate the role of AMP-activated protein kinase (AMPK) activity during endoplasmic reticulum stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-β-D-ribofuranosyl-imidazole-4-​carboxamide and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein β expression levels. [PLoS One] Full Article

PANCREATIC CANCER

Pathophysiological Role of MicroRNA-29 in Pancreatic Cancer Stroma
In an effort to understand the molecular mechanisms associated with tumor-stromal interactions, using in vitro and in vivo models and pancreatic ductal adenocarcinoma patient biopsies, researchers showed that the loss of miR-29 is a common phenomenon of activated pancreatic stellate cells/fibroblasts, the major stromal cells responsible for fibrotic stromal reaction. [Sci Rep] Full Article

Efavirenz Has the Highest Anti-Proliferative Effect of Non-Nucleoside Reverse Transcriptase Inhibitors against Pancreatic Cancer Cells
As other non-nucleoside reverse transcriptase inhibitors (NNRTIs) have not been studied so far, all clinically used NNRTIs were tested and the in vitro toxic concentrations were compared to drug levels in patients to predict possible anti-cancer effects in vivo. [PLoS One] Full Article

Targeting Pancreatic Cancer Cells by a Novel Hydroxamate-Based Histone Deacetylase (HDAC) Inhibitor ST-3595
The authors showed that ST-3595 exerted potent anti-proliferative and cytotoxic activities against both established pancreatic cancer cell lines, and patient-derived primary cancer cells. [Tumor Biol] Abstract

Color-Coding Cancer and Stromal Cells with Genetic Reporters in a Patient-Derived Orthotopic Xenograft (PDOX) Model of Pancreatic Cancer Enhances Fluorescence-Guided Surgery
Researchers used genetic reporters to color code cancer and stroma cells in a PDOX model. The telomerase-dependent green fluorescent protein-containing adenovirus OBP-401 was used to label the cancer cells of a pancreatic cancer PDOX. [Cancer Gene Ther] Abstract

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Resverlogix Officially Attains Phase III Status with a European Regulatory Authority
Resverlogix Corp. announced that following recent meetings with various European regulatory bodies, the first confirmation for their Phase III clinical plan has officially been received. A further regulatory and protocol design update will be provided to the market post the approval of additional regulatory bodies and the launch of the planned Phase III clinical trial entitled BETonMACE. [Resverlogix Corp.] Press Release

Insulin Independence Revolutionary Phase III Trial
Perle Bioscience, Inc. announced enrollment for the Insulin Independence Trial. This trial is the first Phase III trial to test a combination therapy in type 1 diabetics. [Perle Bioscience, Inc.] Press Release

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NEW Research Associate – Cancer Therapeutics (University of Cambridge)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

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Postdoctoral Position – Adipocyte Development (German Institute of Human Nutrition)

Postdoctoral Research Associate – Type 1 Diabetes and Other Autoimmune Diseases (Benaroya Research Institute at Virginia Mason)

PhD Position – Pancreatic Diseases (University Hospital Zurich)

Postdoctoral Position – Metabolic Fingerprinting of Gestational Diabetes Mellitus (CEU San Pablo University)

Postdoctoral Position – Cancer (MD Anderson Cancer Center)

PhD Studentships – Diabetes Research (Diabetes UK)

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