Pancreatic Cell News Volume 5.41 | Oct 28 2014

Antioxidant Signaling Involving the Microtubule Motor KIF12 Is an Intracellular Target of Nutrition Excess in Beta Cells
Researchers demonstrate that the microtubule motor KIF12 mediates an antioxidant cascade in beta cells as an intracellular target of excess fat intake or “lipotoxicity.” KIF12 knockout mice suffer from hypoinsulinemic glucose intolerance due to increased beta cell oxidative stress. [Dev Cell] Abstract | Graphical Abstract

Inhibition of BACE2 Counteracts hIAPP-Induced Insulin Secretory Defects in Pancreatic β-Cells
Researchers found by global gene expression profiling that β-site APP-cleaving enzyme 2 (BACE2) was up-regulated in the rat pancreatic β-cell line INS1E stably transfected with human islet amyloid polypeptide (hIAPP) gene. [FASEB J] Abstract

Pro-Oxidant/Antioxidant Balance Controls Pancreatic β-Cell Differentiation through the ERK1/2 Pathway
Researchers investigated the role of reactive oxygen species (ROS) in β-cell development. Decreasing ROS production in vivo reduced β-cell differentiation. Moreover, in cultures of pancreatic explants, progenitors were highly sensitive to ROS stimulation and responded by generating β-cells. [Cell Death Dis]
Full Article

PDX-1 mRNA-Induced Reprogramming of Mouse Pancreas-Derived Mesenchymal Stem Cells into Insulin-Producing Cells In Vitro
Scientists demonstrated that mouse pancreas-derived mesenchymal stem cells can be transdifferentiated into effective glucose-responsive insulin-producing cells through transfecting synthetic modified PDX-1 mRNA in vitro. [Clin Exp Med] Abstract

Congo Red Modulates ACh-Induced Ca²⁺ Oscillations in Single Pancreatic Acinar Cells of Mice
Recent studies show that congo red exerts neuroprotective effects in a variety of models of neurodegenerative diseases. However, its pharmacological profile remains unknown. In this study, scientists investigated the effects of congo red on ACh-induced Ca²⁺ oscillations in mouse pancreatic acinar cells in vitro. [Acta Pharmacol Sin] Full Article

PANCREATIC CANCER

Extracellular Lumican Inhibits Pancreatic Cancer Cell Growth and Is Associated with Prolonged Survival after Surgery
Primary PDAC cells and recombinant human lumican protein were used to establish a working model to mimic the in vivo interactions between stromal lumican and PDAC cells. Using this model, scientists tested the effects of lumican on EGFR signaling via Akt and HIF-1α and its subsequent influence on glucose consumption, lactate production, intracellular ATP, and apoptotic cell death. [Clin Cancer Res] Abstract

Inhibition of RAC1 GTPase Sensitizes Pancreatic Cancer Cells to G-Irradiation
Researchers show that Rac1 plays a critical role in the response of pancreatic cancer cells to ionizing radiation (IR). Inhibition of Rac1 using specific inhibitor and dominant negative Rac1 mutant not only abrogates IR-induced G2 checkpoint activation, but also increases radiosensitivity of pancreatic cancer cells through induction of apoptosis. [Oncotarget] Full Article

RAGE Is Essential for Oncogenic KRAS-Mediated Hypoxic Signaling in Pancreatic Cancer
Scientists demonstrate that binding of receptor for advanced glycation end products (RAGE) to oncogenic KRAS facilitates hypoxia-inducible factor 1 (HIF1)α activation and promotes pancreatic tumor growth under hypoxic conditions. Hypoxia induces NF-κB-dependent and HIF1α-independent RAGE expression in pancreatic tumor cells. [Cell Death Dis] Full Article

Overexpression of Heat Shock Protein 27 (HSP27) Increases Gemcitabine Sensitivity in Pancreatic Cancer Cells through S-Phase Arrest and Apoptosis
Researchers investigate the underlying mechanisms of HSP27-mediated gemcitabine sensitivity. Utilizing a pancreatic cancer cell model with stable HSP27 overexpression, cell cycle arrest and apoptosis induction were analyzed by flow cytometry, nuclear staining, immunoblotting and mitochondrial staining. [J Cell Mol Med]
Full Article

MicroRNA-100 Regulates Pancreatic Cancer Cells Growth and Sensitivity to Chemotherapy through Targeting FGFR3
The effects of overexpressing microRNA 100 (miR-100) on pancreatic cancer cell proliferation and chemosensitivity to cisplatin were examined by cell proliferation essay in vitro. MIA PaCa-2 cells with endogenously overexpressed miR-100 were transplanted into null mice to examine tumor growth in vivo. [Tumor Biol] Abstract

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Oramed Pharmaceuticals Reports Positive Top-Line Data from U.S. Phase IIa Trial with Oral Insulin in Type 1 Diabetes
Oramed Pharmaceuticals Inc. reported positive top-line clinical results from its Phase IIa clinical trial of ORMD-0801, the company’s proprietary oral insulin capsules, to treat type 1 diabetes. [Oramed Pharmaceuticals Inc.] Press Release

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NEW Associate or Full Professor – Pediatric Diabetes and Metabolic Disease (University of California San Diego)

Postdoctoral Fellowship Position – Obesity and Diabetes Pathogenesis (NIDDK / NIH)

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Research Assistant – Diabetes/Metabolic Health (The Nestlé Institute of Health Sciences)

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Full or Associate Professor – Endocrinology, Diabetes and Metabolism (University of Pennsylvania)

Scientist – Pluripotent Stem Cell Biology Endoderm Lineages (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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