DIABETES & PANCREATITIS β-Cell Insulin Secretion Requires the Ubiquitin Ligase COP1 Scientists showed that post-translational regulation of the transcription factors ETV1, ETV4, and ETV5 by the ubiquitin ligase COP1 (also called RFWD2) in β cells is critical for insulin secretion. [Cell] Abstract | Graphical Abstract Reduced Insulin Production Relieves Endoplasmic Reticulum Stress and Induces β Cell Proliferation Researchers defined the effects of ∼50% reduced insulin production in Ins1−/−:Ins2f/f:Pdx1CreERT:mTmG mice prior to robust hyperglycemia. Transcriptome, proteome, and network analysis revealed alleviation of chronic endoplasmic reticulum stress, indicated by reduced Ddit3, Trib3, and Atf4 expression; reduced Xbp1 splicing; and reduced phospho-eIF2α. [Cell Metab] Abstract | Graphical Abstract Autocrine Selection of a GLP-1R G-Protein Biased Agonist with Potent Antidiabetic Effects The authors report the discovery of the potent and selective glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) G-protein-biased agonist, P5. They showed that P5 promotes G-protein signaling comparable to GLP-1 and Exendin-4, but exhibited a significantly reduced β-arrestin response. [Nat Commun] Full Article | Press Release Acetylation of Glucokinase Regulatory Protein Decreases Glucose Metabolism by Suppressing Glucokinase Activity Scientists demonstrated that glucokinase (GK) regulatory protein (GKRP) is acetylated at Lys5 by the acetyltransferase p300. Acetylated GKRP is resistant to degradation by the ubiquitin-dependent proteasome pathway, suggesting that acetylation increases GKRP stability and binding to GK, further inhibiting GK nuclear export. [Sci Rep] Full Article Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-Induced Acute Pancreatic Injury through Modulating Apoptosis and NF-κB-Mediated Inflammation Results confirmed surfactant protein D (SP-D) expression in pancreatic islets and intercalated ducts and explored the role of pancreatic SP-D in sepsis. Cecal ligation and puncture (CLP) decreased pancreatic SP-D levels and caused severe pancreatic injury with higher serum amylase 24 hours after CLP. [Sci Rep] Full Article Socs1 and Socs3 Degrades Traf6 via Polyubiquitination in LPS-Induced Acute Necrotizing Pancreatitis Data revealed that the level of Traf6 expression was significantly increased in the mild acute pancreatitis induced by cerulein, and the upregulation of Traf6 played a protective role in acinar cells against cerulein-induced apoptosis. [Cell Death Dis] Full Article The Role of ARX in Human Pancreatic Endocrine Specification Aristaless Related Homeobox (ARX) knockout human embryonic stem cells retained pancreatic differentiation capacity and ARX knockout endocrine cells were biased toward somatostatin-positive cells (94% of endocrine cells) with reduced pancreatic polypeptide (rarely detected), glucagon (90% reduced) and insulin-positive (65% reduced) lineages. [PLoS One] Full Article PANCREATIC CANCER ROR Functions as a ceRNA to Regulate Nanog Expression by Sponging miR-145 and Predicts Poor Prognosis in Pancreatic Cancer The authors measured ROR in 61 paired cancerous and noncancerous tissue samples by qRT-PCR and investigated the biological role of ROR on the phenotypes of pancreatic cancer stem cells in vitro and in vivo. [Oncotarget] Full Article Negative Correlation of ITCH E3 Ubiquitin Ligase and miRNA-106b Dictates Metastatic Progression in Pancreatic Cancer Researchers report that ITCH transcript and protein expression mimic metastatic trait in pancreatic cancer patients and cell lines. [Oncotarget] Full Article Differential Regulation of ZEB1 and EMT by MAPK-Interacting Protein Kinases (MNKs) and eIF4E in Pancreatic Cancer Scientists demonstrated that human pancreatic ductal adenocarcinoma cells grown in collagen exhibit increased activation of the MNKs that mediate eIF4E phosphorylation. [Mol Cancer Res] Abstract MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma Gemcitabine-resistant variants of two mutant p53 human pancreatic ductal adenocarcinoma (PDAC) cell lines were established. Both established PDAC clones showed a significant resistance to gemcitabine with low apoptosis rate versus parental cells. [PLoS One] Full Article |