Pancreatic Cell News Volume 8.11 | Mar 21 2017

TOP STORY

Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice

The authors investigated the role of serotonin (5-HT) signaling in the growth of pancreatic tumors. They found levels of 5-HT to be increased in human pancreatic ductal adenocarcinoma (PDAC) tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. [Gastroenterology] Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Progression of Type 1 Diabetes from the Prediabetic Stage Is Controlled by Interferon-α Signaling

Blockade of IFN-α but not IFN-β signaling using either an antibody or a selective S1PR1 agonist, CYM-5442, prevented type 1 diabetes (T1D) in the mouse Rip-LCMV T1D model. [Proc Natl Acad Sci USA] Abstract

Deletion of XIAP Reduces the Severity of Acute Pancreatitis via Regulation of Cell Death and Nuclear Factor-κB Activity

Researchers investigated the potential role of X-linked inhibitor of apoptosis protein (XIAP) in regulation of cell death and inflammation during acute pancreatitis. Deletion of XIAP resulted in the reduction of amylase activity, decrease of nuclear factor-κB activation and less release of TNF-α and IL-6, together with increased caspases activities and receptor-interacting protein kinase1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. [Cell Death Dis] Full Article

The Endoplasmic Reticulum Stress/Autophagy Pathway Is Involved in Cholesterol-Induced Pancreatic β-Cell Injury

Scientists explored the role of the endoplasmic reticulum (ER) stress pathway in cholesterol-induced lipotoxicity. ER stress-associated proteins glucose-regulated protein 78, activating transcription factor 4 and C/EBP homologous protein, and phosphorylation of eukaryotic initiation factor 2α, were all up-regulated by cholesterol. [Sci Rep] Full Article

An Excessive Increase in Glutamate Contributes to Glucose-Toxicity in β-Cells via Activation of Pancreatic NMDA Receptors in Rodent Diabetes

The authors investigated whether endogenous glutamate aggravated β-cell dysfunction under chronic exposure to high-glucose via activation of N-methyl-D-aspartate receptors (NMDARs). Long-term treatment of β-cells with NMDA inhibited cell viability and decreased GSIS. The NMDAR antagonist MK-801 or GluN1 knockout prevented high-glucose-induced dysfunction in β-cells. [Sci Rep] Full Article

Dichotomy between Receptor-Interacting Protein 1- and Receptor-Interacting Protein 3-Mediated Necroptosis in Experimental Pancreatitis

Scientists investigated the expression of necrosome components, including receptor-interacting protein (RIP)1, RIP3, and mixed lineage kinase domain-like (MLKL), and the molecular mechanisms in pancreatitis-associated necroptosis. They found that RIP3 and phosphorylated MLKL expression were positively related to the degree of necrosis, whereas RIP1 expression was negatively related to the degree of necrosis. [Am J Pathol] Abstract

Ultrastructural Alterations of Pancreatic Beta Cells in Human Diabetes Mellitus

Researchers provided a comprehensive ultrastructural analysis of human pancreatic islets in type 1 and type 2 diabetic patients. A lower amount of beta cells was found in both T1D and T2D than in non-diabetic islets, whereas alpha cells were increased only in T2D. [Diabetes Metab Res Rev] Abstract

PANCREATIC CANCER

Increased Semaphorin 3c Expression Promotes Tumor Growth and Metastasis in Pancreatic Ductal Adenocarcinoma by Activating the ERK1/2 Signaling Pathway

Investigators found that aberrant semaphorin 3c (sema3c) expression was positively associated with a particular tumor stage and correlated with poor survival of pancreatic ductal adenocarcinoma (PDAC) patients. Knockdown of sema3c attenuated proliferation, migration, invasion and epithelial–mesenchymal transition in a pancreatic cancer cell line and reduced PDAC cell tumorigenesis upon xenotransplantation into nude mice. [Cancer Lett] Abstract

Oncolytic Adenovirus Expressing Relaxin (YDC002) Enhances Therapeutic Efficacy of Gemcitabine against Pancreatic Cancer

The authors examined the ability of combined treatment with gemcitabine and YDC002, which degrades extracellular matrix, to efficiently treat chemoresistant and desmoplastic pancreatic cancer. Gemcitabine alone exhibited similarly low cytotoxicity toward pancreatic cancer cells throughout the concentration range used, whereas the combination of YDC002 and a subtherapeutic dose of gemcitabine resulted in potent anticancer effects through effective induction of apoptosis. [Cancer Lett] Abstract

Maltotriose Conjugation to a Chlorin Derivative Enhances the Antitumor Effects of Photodynamic Therapy in Peritoneal Dissemination of Pancreatic Cancer

Investigators evaluated the effects of photodynamic therapy with maltotriose-conjugated chlorin (Mal3-chlorin) in culture and in a peritoneal disseminated mice model of pancreatic cancer. In vitro, Mal3-chlorin showed superior uptake into pancreatic cancer cells compared with talaporfin, which is clinically used. [Mol Cancer Ther] Abstract

Improving Glycemic Control in Type 2 Diabetes: Stimulate Insulin Secretion or Provide Beta-Cell Rest?

Researchers argue that strategies that induce beta-cell rest have considerable potential to preserve long-term beta-cell function. This is based on laboratory-based studies involving human islets as well as clinical studies employing intensive insulin therapy, thiazolidinediones, bariatric surgery, short-acting glucagon-like peptide-1 receptor agonists, and a promising new class of diabetes drugs, sodium-glucose linked transporter-2 inhibitors. [Diabetes Obes Metab] Abstract

Exploring Inter-Organ Crosstalk to Uncover Mechanisms that Regulate β-Cell Function and Mass

The microbiome and the immune system are emerging as important players in regulating β-cell function and mass. The rich innervation of islet cells indicates it is a prime organ for regulation by the nervous system. The authors discuss the potential implications of signals from these organ systems as well as those from bone, placenta, kidney, thyroid, endothelial cells, reproductive organs and adrenal and pituitary glands that can directly impact β-cell biology. [Eur J Clin Nutr] Abstract

The Role of Plant-Derived Products in Pancreatitis: Experimental and Clinical Evidence

Scientists review various plant products screened for the treatment of pancreatitis. The possible mechanistic profile of these phytochemicals is summarized. [Phytother Res] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.

Glycyx PharmaVentures and Valeant Pharmaceuticals Agree to Binding Terms of Licensing Agreement in the Field of Oncology

Glycyx PharmaVentures Ltd. has agreed to enter into an exclusive license agreement with Valeant Pharmaceuticals International, Inc., pursuant to which Valeant will grant to Glycyx a license or sublicense to develop and commercialize products containing methylnaltrexone bromide for oncology indications in countries outside the US and Canada. [Glycyx PharmaVentures Ltd.] Press Release

National Institutes of Health Awards UMass Dartmouth Researcher $616,170 to Study How Type 2 Diabetes Increases Risk of Bone Fractures

The National Institutes of Health has awarded UMass Dartmouth Assistant Professor of Bioengineering Lamya Karim a $616,170 grant to study how type 2 diabetes weakens bones and results in patients being at much greater risk for fractures. [The University of Massachusetts] Press Release

Research Is an Afterthought in First Trump Budget

The 2018 budget proposal that President Donald Trump unveiled confirms two things that U.S. scientists have long suspected: The new president is no fan of research, and his administration has no overarching strategy for funding science. Deep proposed cuts to research at the National Institutes of Health, the Department of Energy, the U.S. Geological Survey, the Environmental Protection Agency, and the National Oceanic and Atmospheric Administration offer evidence that Trump doesn’t see science — of any kind — as a spending priority. [ScienceInsider] Editorial

Jailed Iranian Researcher’s Health Worsening Rapidly

An Iranian researcher jailed in Tehran for the last 11 months is in declining health after spending more than two months on hunger strike. This month, researchers around the world made urgent appeals for his release. [Nature News] Editorial

Trump’s NIH Budget May Include Reducing Overhead Payments to Universities

The Trump administration may be planning to help pay for a massive 18% cut to the National Institutes of Health (NIH) by slashing payments to universities and research institutes for overhead costs, ScienceInsider has learned. [ScienceInsider] Editorial

NEW 12^th Biennial Regional Congress of the European-African Hepato-Pancreato-Biliary Association
May 23-26, 2017
Mainz, Germany

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Fellow – Pancreatic Cancer Immunology (Memorial Sloan Kettering)

NEW Postdoctoral Positions – Life Sciences (Helmholtz Zentrum München)

NEW Associate Program Officer – Type 1 Diabetes (Helmsley Charitable Trust)

Senior Scientist – Pancreatic Cell Research (STEMCELL Technologies Inc.)

Postdoctoral Fellows – Diabetes Research (Icahn School of Medicine at Mount Sinai)

Bioinformatician/ Data Analyst – Beta Cell Biology (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

Postdoctoral Fellow – Beta Cell Biology (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

Research Positions – Mouse Genetics, Diabetes and Reprogramming (Inserm)

Postdoctoral Associate – Human Pancreatic Stem Cells (Nestlé)

Postdoctoral Fellowship – Beta Cell Regeneration (Helmholtz Zentrum München)

Postdoctoral Fellows – Cancer Epigenetics (Baylor Scott & White Research Institute)

Postdoctoral Position – Pancreatic Cancer (Cold Spring Harbor Laboratory)

Postdoctoral Fellow – Islet Function/Regeneration (Toronto General Research Institute)

Principle Scientist – Translational Development (Celgene Corporation)

Assistant Professor – Molecular Therapeutics (Dartmouth College/Geisel School of Medicine)

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