DIABETES & PANCREATITIS CK2 Acts as a Potent Negative Regulator of Receptor-Mediated Insulin Release In Vitro and In Vivo The potential physiological relevance of β-Cell M3 muscarinic receptors (M3Rs) phosphorylation (or of G protein-coupled receptors in general) by casein kinase 2 (CK2) remains unknown. The authors showed that CK2-dependent phosphorylation of β-cell M3Rs significantly impairs M3R-mediated increases in insulin release in vitro and in vivo. [Proc Natl Acad Sci USA] Abstract O-Linked β-N-Acetylglucosamine (O-GlcNAc) Acts as a Glucose Sensor to Epigenetically Regulate the Insulin Gene in Pancreatic Beta Cells Using directed pharmacological approaches in the mouse insulinoma-6 cell line, researchers demonstrated that elevating nuclear O-GlcNAc increases intracellular insulin levels and preserves glucose stimulated insulin secretion during chronic hyperglycemia. [J Biol Chem] Full Article SPECT of Transplanted Islets of Langerhans by Dopamine 2 Receptor Targeting in a Rat Model Since islets express dopamine 2 (D2) receptors, they could be visualized by targeting this receptor. Therefore, the D2 receptor antagonist based tracer [125/123I][IBZM] was selected to visualize transplanted islets in a rat model. [Mol Pharm] Abstract GSK-3β Mediates Dexamethasone-Induced Pancreatic β Cell Apoptosis The effect of dexamethasone treatment on rat pancreatic β-cell line (INS-1) apoptosis (determined by TUNEL and Flow Cytometry), generation of reactive oxidative stress, and the phosphorylation status of glycogen synthase kinase-3β (GSK-3β) was determined. The inhibitory effect of GSK-3β inhibitor-lithium chloride on dexamethasone-induced β-cell apoptosis was also evaluated. [Life Sci] Abstract PANCREATIC CANCER Regulation of Oncogenic KRAS Signaling via a Novel KRAS-Integrin-Linked Kinase-hnRNPA1 Regulatory Loop in Human Pancreatic Cancer Cells On the basis their finding that knockdown of either KRAS or ILK has a reciprocal effect on the other’s expression, the authors hypothesized the presence of an ILK-KRAS regulatory loop that enables pancreatic cancer cells to regulate KRAS expression. [Oncogene] Abstract Development of a Panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-Systematic Evolution of Ligands by EXponential enrichment (SELEX) targeting human pancreatic ductal adenocarcinoma. [Sci Rep] Full Article Tumor-Selective Use of DNA Base Excision Repair Inhibition in Pancreatic Cancer Using the NQO1 Bioactivatable Drug, β-Lapachone Targeting base excision repair (BER) alone has limited therapeutic potential for pancreatic or other cancers due to a general lack of tumor-selectivity. The authors present a treatment strategy that makes BER inhibition tumor-selective and NAD(P)H:Quinone Oxidoreductase 1-dependent for therapy of most solid neoplasms, particularly for pancreatic cancer. [Sci Rep] Full Article Pivotal Role of the Chromatin Protein Nupr1 in Kras-Induced Senescence and Transformation Nupr1 is a chromatin protein, which cooperates with KrasG12D to induce PanIN formation and pancreatic cancer development in mice, though the molecular mechanisms underlying this effect remain to be fully characterized. The authors report that Nupr1 acts as a gene modifier of the effect of KrasG12D-induced senescence by regulating Dnmt1 expression and consequently genome-wide levels of DNA methylation. [Sci Rep] Full Article The P2X7 Receptor Regulates Cell Survival, Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells The authors determined the expression (real time PCR and Western blot) and localization (immunofluorescence) of P2X7R in human pancreatic ductal adenocarcinoma cell lines and a “normal” human pancreatic duct epithelial cell line. The function of P2X7R in proliferation (BrdU assay), migration (wound assay) and invasion (Boyden chamber with matrigel) was characterized. [Mol Cancer] Full Article Minnelide Effectively Eliminates CD133+ Side Population in Pancreatic Cancer Results indicated that triptolide enhanced and enriched the “stemness” in pancreatic ductal adenocarcinoma cell lines at a low dose of 12.5 nM, but also resulted in the regression of tumors derived from these cells. [Mol Cancer] Full Article |