DIABETES Potential of Protein Phosphatase Inhibitor 1 As Biomarker of Pancreatic Beta Cell Injury In Vitro and In Vivo Investigators proposed protein phosphatase 1, regulatory (inhibitor) subunit 1A (PPP1R1A) as novel biomarker for acute beta cell destruction. LC-MS/MS proteome analysis of FACS-purified beta cells, tissue-comparative Western blotting and immunohistochemistry indicated relatively high molar abundance and selectivity of PPP1R1A in beta cells. [Diabetes] Abstract Microarray Analysis of Novel Candidate Genes Responsible for Glucose-Stimulated Insulin Secretion in Mouse Pancreatic β Cell Line MIN6 Researchers previously isolated a subclone, MIN6 clone 4, from the parental MIN6 cells, that shows well-regulated insulin secretion in response to glucose, glybenclamide, and KCl, even after prolonged culture. To investigate the molecular mechanisms responsible for preserving glucose-stimulated insulin secretion in this subclone, they compared four groups of MIN6 cells: Pr-LP (parental MIN6, low passage number), Pr-HP (parental MIN6, high passage number), C4-LP (MIN6 clone 4, low passage number), and C4-HP (MIN6 clone 4, high passage number). [PLoS One] Full Article PARP-1 and YY1 Are Important Novel Regulators of CXCL12 Gene Transcription in Rat Pancreatic Beta Cells The roles of poly(ADP-ribose) polymerase-1 (PARP-1) and transcription factor Yin Yang 1 (YY1) in Cxcl12 transcription were studied by examining their in vitro and in vivo binding affinities for the Cxcl12 promoter in a pancreatic beta cell line by the electrophoretic mobility shift assay and chromatin immunoprecipitation. Experimental evidence for PARP-1 and YY1 revealed their trans-acting potential, wherein PARP-1 displayed an inhibitory, and YY1 a strong activating effect on Cxcl12 transcription. [PLoS One] Full Article Targeted Overexpression of CKI-Insensitive Cyclin-Dependent Kinase 4 Increases Functional β-Cell Number Through Enhanced Self-Replication in Zebrafish Researchers tested the hypothesis that insufficient activity of cyclin-dependent kinase 4 may be responsible for the low replication rate by ectopically expressing in β-cells a mutant CDK4 (CDK4R24C) that is insensitive to inhibition by cyclin-dependent kinase inhibitors. [Zebrafish] Abstract GLP-1 Could Improve the Similarity of Insulin-Producing Cells from Human Adipose Tissue-Derived Mesenchymal Stem Cells and Pancreatic Beta Cells in Cellular Ultrastructure and Function The authors suggested that insulin-producing cells (IPCs) could not mimic the physiological regulation of insulin secretion performed by pancreatic beta cells. To obtain a better method through which to acquire more similar IPCs, they compared the difference between IPCs of the glucagon-like peptide-1 (GLP-1) group and IPCs of the non-GLP-1 group in the morphological features in cellular level and physiological function. [J Cell Biochem] Abstract PANCREATIC CANCER Pancreatic Tumors Escape from Translational Control through 4E-BP1 Loss Scientists report that pancreas expresses specifically and massively 4E-BP1 (4E-BP2 is nearly undetectable). However, 4E-BP1 expression is extinguished in more than half of the human pancreatic ductal adenocarcinomas. [Oncogene] Abstract ERK2-Regulated TIMP1 Induces Hyperproliferation of K-Ras G12D-Transformed Pancreatic Ductal Cells Researchers investigated the specific genes downstream of MAPK-ERK2 responsible for the hyperproliferative abilities of human and murine primary ductal epithelial cells (PDCs) within an extracellular matrix. Compared with control, DNA synthesis and total cell proliferation was significantly increased in human PDCs harboring the pancreatic ductal adenocarcinoma-common p53, Rb/p16INK4a, and K-RasG12D mutations. [Neoplasia] Abstract | Full Article Evaluation of the Potential Therapeutic Role of a New Generation of Vitamin D Analog, MART-10, in Human Pancreatic Cancer Cells In Vitro and In Vivo Scientists investigated the effectiveness and safety of a new generation, less calcemic analog of 1α,25(OH)2D3, 19-nor-2α-(3-hydroxypropyl)-1α,25-dihydroxyvitamin D3 (MART-10), in BxPC-3 human pancreatic carcinoma cells in vitro and in vivo. [Cell Cycle] Abstract Stem Cell Marker Nestin Is Critical for TGF Beta1-Mediated Tumor Progression in Pancreatic Cancer Researchers showed that nestin overexpression in PDAC cells increased cell motility and drove phenotypic changes associated with the epithelial-mesenchymal transition in vitro; conversely, knockdown of endogenous nestin expression reduced the migration rate, and cells reverted to a more epithelial phenotype. [Mol Cancer Res] Abstract | Full Article Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells Spongiatriol, a marine furanoditerpenoid that was first isolated in the 1970s, is shown here to inhibit Nuclear Factor Kappa B (NFκB) transcriptional activity in a reporter cell line, to reduce levels of phosphorylated (active) NFκB in the AsPC-1 cell line, to have an IC50 for cytotoxicity in the low micromolar range against the AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1 pancreatic cancer cell lines, and to induce moderate but significant apoptosis in both the AsPC-1 and the Panc-1 cell lines. [Mar Drugs] Abstract | Full Article |