Pancreatic Cell News Volume 7.01 | Jan 12 2016

Human Pancreatic Beta-Like Cells Converted from Fibroblasts
Pancreatic beta cells are of great interest for biomedical research and regenerative medicine. Scientists showed the conversion of human fibroblasts towards an endodermal cell fate by employing non-integrative episomal reprogramming factors in combination with specific growth factors and chemical compounds. [Nat Commun] Full Article

Identification of a Mammalian Glycerol-3-Phosphate Phosphatase: Role in Metabolism and Signaling in Pancreatic β-Cells and Hepatocytes
Scientists observed that glycerol-3-phosphate phosphatase (G3PP) expression level controls glycolysis, lipogenesis, lipolysis, fatty acid oxidation, cellular redox, and mitochondrial energy metabolism in β-cells and hepatocytes, as well as glucose-induced insulin secretion and the response to metabolic stress in β-cells, and in gluconeogenesis in hepatocytes. [Proc Natl Acad Sci USA] Abstract

Growth Factors and Medium Hyperglycemia Induce Sox9⁺ Ductal Cell Differentiation into Beta Cells in Mice with Reversal of Diabetes
Using lineage-tracing with genetic labeling of Insulin- or Sox9-expressing cells, the authors showed that hyperglycemia is required for inducing Sox9⁺ ductal cell differentiation into insulin-producing β cells, and medium hyperglycemia in combination with long-term administration of low-dose epidermal growth factor synergistically augments differentiation and is associated with normalization of blood glucose in nonautoimmune diabetic C57BL/6 mice. [Proc Natl Acad Sci USA] Abstract

ECM Signaling Regulates Collective Cellular Dynamics to Control Pancreas Branching Morphogenesis
Researchers employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. They observed that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; additionally, they largely remain in the outer cell compartment even after mitosis. [Cell Rep] Abstract | Graphical Abstract | Full Article

Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights
Researchers aimed to identify anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. [Sci Rep] Full Article

Pterostilbene Ameliorates Streptozotocin-Induced Diabetes through Enhancing Antioxidant Signaling Pathways Mediated by Nrf2
The authors investigated the antidiabetic role of pterostilbene (PTS) in streptozotocin (STZ)-induced diabetic model through nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant mechanisms. The ability of PTS to activate Nrf2 in MIN6 cells was assessed by dissociation of the Nrf2-Keap1 complex at different time points and by expression of ARE-driven downstream target genes of Nrf2. [Chem Res Toxicol] Abstract

Osteoprotegerin Regulates Pancreatic Beta-Cell Homeostasis Upon Microbial Invasion
Investigators treated mice with lipopolysaccharide (LPS) and observed osteoprotegerin (OPG) production in the pancreas, especially in β-cells of pancreatic islets. Insulin release following LPS administration was enhanced in mice lacking OPG, suggesting that OPG inhibits insulin secretion under acute inflammatory conditions. [PLoS One] Full Article

PANCREATIC CANCER

Mutant p53 Determines Pancreatic Cancer Poor Prognosis to Pancreatectomy Through Upregulation of Cavin-1 in Patients with Preoperative Serum CA19-9 ≥ 1,000 U/mL
Scientists elucidated the relationship between this signature and driver-gene mutations, and the cavins/caveolin-1 axis. Four major driver-genes (KRAS, TP53, CDKN2A/p16, and SMAD4/DPC4) that are associated with pancreatic ductal adenocarcinoma and five critical molecules (cavin-1/-2/-3/-4 and caveolin-1) in the cavins/caveolin-1 axis were screened by immunohistochemistry in tumor tissue microarrays. [Sci Rep] Full Article

The CaSm (LSm1) Oncogene Promotes Transformation, Chemoresistance and Metastasis of Pancreatic Cancer Cells
The authors demonstrated that cancer-associated Sm-like (CaSm) overexpression alters several hallmarks of cancer-including transformation, proliferation, chemoresistance and metastasis. Doxycycline-induced CaSm expression enhanced proliferation and both anchorage-dependent and -independent growth of the human Panc-1 cells in vitro. [Oncogenesis] Full Article

IL-6/STAT3 Plays a Regulatory Role in the Interaction between Pancreatic Stellate Cells and Cancer Cells
Pancreatic stellate cells (PSCs) treated with conditioned medium of immortalized human cells (PSC-CM) induced the activation of signal transducers and activator of transcription 3 (STAT3) in pancreatic cancer cells. Neutralization of IL-6 suppressed the PSC-CM-induced upregulation of genes including complement factor B, lipocalin, and chemokine (C-C motif) ligand 20. [Dig Dis Sci] Abstract

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BioLineRx Announces Collaboration With MSD to Investigate the Combination of KEYTRUDA® (Pembrolizumab) and BL-8040 in Pancreatic Cancer
BioLineRx Ltd. announced a collaboration with MSD, known as Merck in the United States and Canada, to support a Phase II study investigating BioLineRx’s BL-8040 in combination with KEYTRUDA^® (pembrolizumab), MSD’s anti-PD-1 therapy, in patients with metastatic pancreatic cancer. [BioLineRx Ltd.] Press Release

Baxalta Announces Priority Review Status Granted by Health Canada for Irinotecan Liposome Injection (nal-IRI) for New Drug Submission
Baxalta Incorporated announced that Health Canada has granted Priority Review status for its New Drug Submission for irinotecan liposome injection, also known as “nal-IRI”. Baxalta is seeking marketing approval of nal-IRI from Health Canada for the treatment of patients with metastatic adenocarcinoma of the pancreas previously treated with gemcitabine-based therapy. [Baxalta Incorporated] Press Release

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NEW Post-Doc Fellowship – Diabetes Research (Sanford Research/University of South Dakota)

NEW Faculty Position – Biomedical Metabolomics & Metabolism (University of Ottawa)

Post-Doc Researcher – Pancreatic Cancer (The Walter and Eliza Hall Institute of Medical Research)

Visiting Scientist – Diabetes (Danish Diabetes Academy)

Post-Doc Researcher – Type 1 Diabetes (University of Turku)

Principal Investigator – Age Related Disease (Austrian Institute of Technology)

Post-Doc Researcher – Functional Genomics of Obesity (Inserm)

Clinical Research Fellow – Pancreatic Ductal Adenocarcinoma (Imperial College London)

MD/PhD Researcher – Biomedical Sciences (Hannover Medical School)

PhD Studentship – Cancer Biology (University of Salzburg)

Post-Doc Fellowship (German Cancer Research Center)

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