Pancreatic Cell News 8.22 June 6, 2017 | |
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TOP STORYNewly Discovered Disease Mechanism for Type 2 Diabetes It has long been known that the insulin-producing cells fail in type 2 diabetes. The body does not get enough insulin and blood sugar rises. One theory argues that the insulin-producing cells become fewer in number, while another argues that their function is impaired. Invesigators describe a new explanation, which combines the debated theories, states that the insulin-producing cells regress in their development and become immature. This reduces the number of functional cells. [Press release from University of Gothenburg discussing online prepublication in Nature Communications] Press Release | Full Article | |
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PUBLICATIONS(Ranked by impact factor of the journal)DIABETES & PANCREATITISThe authors examined the role of aquaporin (AQP) 7, the main glycerol channel in β-cells, and AQP12, an aquaporin related to pancreatic damage, in the improvement of pancreatic function and steatosis after sleeve gastrectomy in diet-induced obese rats. AQP7 upregulation in β-cells after sleeve gastrectomy contributed, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol used for insulin release triggered by GLP-1, rather than for ghrelin-induced triacylglycerol biosynthesis. [Int J Obesity] Abstract GLP-1 Receptor Signaling Promotes β-Cell Glucose Metabolism via mTOR-Dependent HIF-1α Activation Scientists addressed the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) signaling could modulate glucose uptake and utilization in β-cells. They assessed various metabolic parameters after short and long exposure of clonal BRIN-BD11 β-cells and rodent islets to the GLP-1R agonist Exendin-4. They report that prolonged stimulation of the GLP-1R for 18 hours promoted metabolic reprogramming of β-cells. [Sci Rep] Full Article The Prolyl Isomerase Pin1 Increases β Cell Proliferation and Enhances Insulin Secretion To elucidate the role of Pin1 in pancreatic β cells, researchers generated β cell-specific Pin1 KO (βPin1 KO) mice. These mutant mice showed exacerbation of glucose intolerance but had normal insulin sensitivity. They identified two independent factors underlying impaired insulin secretion in the βPin1 KO mice. Pin1 enhanced pancreatic β cells proliferation, as indicated by a reduced β-cell mass in βPin1 KO mice compared with control mice. [J Biol Chem] Abstract | Full Article Investigators demonstrated that microRNA (miR)-144-3p was decreased in pancreatic cancer (PC) tissues and PANC-1 cells, whereas proline-rich protein 11 was remarkably increased. miR-144-3p mimics were discovered to inhibit cell proliferation by arresting cells at the S-phase of the cell cycle, and inducing cell apoptosis in PANC-1 cells. The effects of miR-144-3p on cell proliferation and cell apoptosis were reversed after treatment with the miR-144-3p inhibitor. [DNA Cell Biol] Abstract PANCREATIC CANCERPancreatic Cancer Heterogeneity and Response to Mek Inhibition Using different experimental models, including patient-derived xenografts (PDXs), scientists gauged the efficacy of therapies aimed at two hallmark lesions of pancreatic cancers (PCs): activation of signaling pathways by oncogenic KRAS and inactivation of tumor-suppressor genes. Although the drug targeting inactivation of tumor suppressors by DNA methylation had little effect, the inhibition of Mek, a K-Ras effector, in combination with the standard of care (chemotherapy consisting of gemcitabine/nab-paclitaxel), reduced the growth of three out of five PC-PDXs and impaired metastasis. [Oncogene] Abstract Investigators elucidated the role of M2 isoform of pyruvate kinase (PKM2) in pancreatic cancer progression and the potential of PKM2 as a therapeutic target. They observed that PKM2 was highly expressed in patients with pancreatic cancer and was correlated to survival. To test the potential effects of downregulating PKM2 as a clinical therapy, they constructed an RGD-modified oncolytic adenovirus containing shPKM2 to knock down PKM2 in pancreatic cancer cells. [Cell Death Dis] Full Article Substrate Rigidity Controls Activation and Durotaxis in Pancreatic Stellate Cells The authors demonstrated that matrix stiffness regulates activation and mechanotaxis in pancreatic stellate cells (PSCs). They showed the ability of PSCs to undergo phenotypic transition solely as a result of changes in extracellular matrix stiffness, whilst observing the ability of PSCs to durotactically respond to stiffness variations within their local environment. [Sci Rep] Full Article Researchers found family with sequence similarity 83, member A (FAM83A) was significantly overexpressed and associated with poorer overall survival and disease-free survival in pancreatic cancer. Overexpression of FAM83A markedly promoted, whereas inhibition of FAM83A decreased, cancer stem cell-like traits and chemoresistance both in vitro and in an in vivo mouse model of pancreatic cancer. [Oncogenesis] Full Article Vesicular stomatitis virus (VSV) tumor tropism is generally dependent on the permissiveness of malignant cells to viral replication, rather than on receptor specificity, with several ubiquitously expressed cell-surface molecules to play a role in VSV attachment to host cells. However, as VSV attachment to pancreatic ductal adenocarcinoma (PDAC) cells has never been tested before, investigators examined if it was possibly inhibited in resistant PDACs. Their data showed a dramatically weaker attachment of VSV to HPAF-II, the most resistant human PDAC cell line. [J Virol] Abstract The authors investigated the in vitro cytotoxic effect of the oncolytic vaccinia virus GLV-1h68 combined with dual chemotherapy with nab-paclitaxel plus gemcitabine in four human pancreatic adenocarcinoma cell lines. This chemovirotherapeutic protocol resulted in enhanced tumor cell killing in two tumor cell lines compared to the respective monotherapies. [Mol Ther Oncolytics] Full Article | |
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REVIEWSThe authors review the available literature on sodium-glucose co-transporter 2 (SGLT2) inhibitor-insulin combination therapy and underscore the issues that should be considered prior to introducing SGLT2 inhibitors to individuals with type 2 diabetes who are already on insulin (with or without other antihyperglycemic agents) to ensure individualization of therapy. [Can J Diabetes] Abstract Visit our reviews page to see a complete list of reviews in the pancreatic cell research field. | |
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SCIENCE NEWSExperimental Drug Makes Some Pancreatic Cancers More Vulnerable to Chemo Dr. Sunil Hingorani presented the results of a Phase II trial of an experimental drug. In certain metastatic pancreatic cancer patients, Hingorani reported, adding the drug to a standard chemo regimen lengthened the time patients had before their cancer progressed by an average of four months. [Press release from Fred Hutchinson Cancer Research Center presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release MabVax Therapeutics Holdings, Inc. reported results from its Phase I clinical trial of MabVax’s therapeutic antibody MVT-5873, being evaluated to treat patients with advanced pancreatic cancer and other CA19-9 positive cancers in a poster presentation. [Press release from MabVax Therapeutics Holdings, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release ARMO BioSciences, Inc. announced clinical data on its lead investigational immuno-oncology drug AM0010 in combination with FOLFOX chemotherapy for the treatment of patients with advanced pancreatic cancer. [Press release from ARMO BioSciences, Inc. discussing research presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release Lexicon Pharmaceuticals to Present New Clinical Data Lexicon Pharmaceuticals, Inc. announced that new efficacy and safety data for its investigational drug, sotagliflozin will be presented, including two late-breaking abstracts from the inTandem2 and JDRF studies. [Press release from Lexicon Pharmaceuticals, Inc. discussing research to be presented at the 77th American Diabetes Association (ADA) Scientific Sessions, San Diego] Press Release | |
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INDUSTRY NEWSMabVax Therapeutics Holdings, Inc. announced it entered into a sponsored research agreement with Memorial Sloan Kettering Cancer Center for the development of novel chimeric antigen receptor (CAR) T-cell therapeutics using antibody targeting sequences derived from MabVax’s fully-human antibodies for pancreatic, small cell lung, and other solid tumor cancers. [MabVax Therapeutics Holdings, Inc] Press Release POXEL SA announced additional results from the Imeglimin Phase IIb study conducted in Japan. In addition to the highly statistically significant top-line results for the primary and key secondary endpoint, the company is reporting additional data from this study. [Poxel SA] Press Release | |
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POLICY NEWSRomania’s Science Reforms Prompt Boycott Researchers in Romania are stepping up protests against controversial government science reforms. Hundreds of scientists at leading research institutions say they will refuse to sit on national panels that assess and award grants, after the Romanian researchers’ association Ad Astra called for the boycott. But not all scientists in the country support the move. [Nature News] Editorial NIH Plan to Reduce Overhead Payments Draws Fire President Donald Trump’s administration has brought a long-simmering debate over how the U.S. government supports university research back to a boil. In its 2018 budget proposal, the White House proposes cutting so-called indirect cost payments that the National Institutes of Health (NIH) makes to universities, hospitals, and research institutes by about two-thirds, to 10% of each grant. The administration says the change would allow it to redirect about $4.6 billion now spent each year on overhead—including maintaining labs and complying with regulations—to research. [ScienceInsider] Editorial
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JOB OPPORTUNITIESNEW Postdoctoral Research Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center) PhD Position – Health/Biomedical Sciences (University of Auckland) Postdoctoral Position – Metabolic Regulation of Embryonic and Stem Cells (Joslin Diabetes Center) Postdoctoral Fellowship – Diabetes UK (Diabetes UK) PhD Studentship – Diabetes UK (Diabetes UK) Postdoctoral Fellow – Diabetes (University of Toronto) Faculty Member – Endocrinology, Diabetes and Metabolism (Johns Hopkins University) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Pancreatic Cell News Volume 8.22 | Jun 6 2017