DIABETES & PANCREATITIS Role of KATP Channels in Glucose-Regulated Glucagon Secretion and Impaired Counterregulation in Type 2 Diabetes Investigators showed that α cell KATP-channel activity is very low under hypoglycemic conditions and that hyperglycemia, via elevated intracellular ATP/ADP, leads to complete inhibition. [Cell Metab] Full Article | Graphical Abstract Long-Term IKK2/NF-κB Signaling in Pancreatic β-Cells Induces Immune-Mediated Diabetes Mellitus To investigate the potential diabetogenic effects of NF-κB in β-cells, scientists generated a gain-of-function model allowing conditional IKK2/NF-κB activation in β-cells. [Diabetes] Abstract Identification and Characterization of Glucagon-Like Peptide-1 Receptor Expressing Cells Using a New Transgenic Mouse Model Using newly-generated glp1r-cre mice crossed with fluorescent reporter strains, researchers showed that major sites of glucagon-like peptide-1 receptor glp1r expression include pancreatic β and δ-cells, vascular smooth muscle, cardiac atrium, gastric antrum/pylorus, enteric neurons and vagal and dorsal root ganglia. [Diabetes] Abstract Ectopic Ptf1a Expression in Murine ESCs Potentiates Endocrine Differentiation and Models Pancreas Development In Vitro Scientists derived and characterized a mouse embryonic stem cells (ESCs) line with tetracycline-inducible expression of pancreas-specific transcription factor 1a (PTF1a). They found that transient ectopic expression of PTF1a initiated the pancreatic program in differentiating ESCs causing cells to activate pancreatic duodenal homeobox 1 expression in bud-like structures resembling pancreatic primordia in vivo. [Stem Cells] Abstract Rhein, a Natural Anthraquinone Derivative, Attenuates the Activation of Pancreatic Stellate Cells and Ameliorates Pancreatic Fibrosis in Mice with Experimental Chronic Pancreatitis In cultured pancreatic stellate cells, researchers demonstrated that the expression levels of transforming growth factor-beta-stimulated fibrogenic markers including alpha-smooth muscle actin, fibronectin 1 and type I collagen as well as sonic hedgehog were all notably suppressed by the application of rhein at 10 μM. [PLoS One] Full Article PANCREATIC CANCER Role of CYB5A in Pancreatic Cancer Prognosis and Autophagy Modulation The role of CYB5A was tested in 11 pancreatic ductal adenocarcinoma cell lines and five primary cultures through retrovirus-mediated upregulation and small interfering RNA using wound-healing, invasion, annexin-V, electron microscopy, and autophagic assays, as well as autophagy genes and kinases arrays. [J Natl Cancer Inst] Abstract Mapk Signaling Is Required for Dedifferentiation of Acinar Cells and Development of Pancreatic Intraepithelial Neoplasia in Mice Scientists investigated whether mitogen-activated protein kinase (Mapk) signaling is required for the initiation and maintenance of pancreatic carcinogenesis in mice. In inducible-KrasG12D and p48Cre mice, Mapk signaling is required for the initiation and maintenance of pancreatic cancer precursor lesions. [Gastroenterology] Abstract Mutant KRAS Is a Druggable Target for Pancreatic Cancer Treatment of pancreatic ductal adenocarcinoma cells with siG12D Local Drug EluteR (LODER) resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial-mesenchymal transition. [Proc Natl Acad Sci USA] Abstract Hypoxia-Independent Gene Expression Mediated by Sox9 Promotes Aggressive Pancreatic Tumor Biology Transcriptomic profiles were compared between the non-metastatic pancreatic cancer cell line FG and its angiogenic/metastatic derivate L3.6pl under normoxic or hypoxic conditions. Cluster analysis revealed a number of transcripts that were induced by hypoxia in non-metastatic cancer cells. [Mol Cancer Res] Abstract Role of the Hypoxia-Inducible Factor-1 Alpha Induced Autophagy in the Conversion of Non-Stem Pancreatic Cancer Cells into CD133+ Pancreatic Cancer Stem-Like Cells Recently, several researchers proposed that non-stem cancer cells can convert to stem-like cells to maintain equilibrium. The present study focuses on whether non-stem pancreatic cancer cells can convert to stem-like cells and the role of HIF-1alpha and autophagy in modulating this conversation. [Cancer Cell Int] Abstract | Full Article |