Pancreatic Cell News Volume 8.18 | May 9 2017

TOP STORY

Recurrent Noncoding Regulatory Mutations in Pancreatic Ductal Adenocarcinoma

Investigators used the Genomic Enrichment Computational Clustering Operation to analyze somatic noncoding alterations in 308 pancreatic ductal adenocarcinomas (PDAs) and identify commonly mutated regulatory regions. They found recurrent noncoding mutations to be enriched in PDA pathways, including axon guidance and cell adhesion, and newly identified processes, including transcription and homeobox genes. [Nat Genet] Abstract | Press Release | Video

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Glucose Sensing by Skeletal Myocytes Couples Nutrient Signaling to Systemic Homeostasis

The authors identified the Baf60c-Deptor-AKT pathway as a target of muscle glucose sensing that augments insulin action in skeletal myocytes. Genetic activation of this pathway improved postprandial glucose disposal in mice, whereas its muscle-specific ablation impaired insulin action and led to postprandial glucose intolerance. [Mol Cell] Abstract | Graphical Abstract

Genetic Disruption of Adenosine Kinase in Mouse Pancreatic β-Cells Protects against High Fat Diet-Induced Glucose Intolerance

Researchers evaluated whether adenosine kinase (ADK) disruption in mouse β-cells impacts β-cell mass and/or protects against high fat diet-induced glucose dysregulation. Mice targeted at the Adk locus were bred to Rip-Cre and Ins1-Cre/ERT^1Lphi mice to enable constitutive and conditional disruption of ADK expression in β-cells, respectively. [Diabetes] Abstract

MSC-Derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis

The authors investigated the therapeutic potential of mesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EVs) using their established mouse models for autoimmune diseases affecting the pancreas and the eye: type 1 diabetes (T1D) and uveoretinitis (EAU). The data demonstrated that MSC-derived EVs effectively prevented the onset of disease in both T1D and EAU. [Stem Cell Reportss] Full Article

Development of a Novel Zebrafish Model for Type 2 Diabetes Mellitus

Scientists created diet-induced obesity (DIO) zebrafish using a different method to induce type 2 diabetes mellitus. Zebrafish were overfed a commercially available fish food using an automated feeding system. They monitored the fasting blood glucose levels in the normal-fed group and overfed group over an eight-week period. The fasting blood glucose level was significantly increased in DIO zebrafish compared with that of normal-fed zebrafish. [Sci Rep] Full Article

Glial Cell-Line Derived Neurotrophic Factor Protects Human Islets from Nutrient Deprivation and Endoplasmic Reticulum Stress Induced Apoptosis

Researchers showed that glial cell-line derived neurotrophic factor (GDNF) significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin:insulin ratio in nutrient deprived human islets. GDNF alleviated thapsigargin-induced endoplasmic reticulum stress evidenced by reduced expressions of IRE1α and BiP and consequently apoptosis. This was associated with an increase in phosphorylation of the PI3K/AKT and the GSK3B signaling pathway. [Sci Rep] Full Article

Durable Control of Autoimmune Diabetes in Mice Achieved by Intraperitoneal Transplantation of “Neo-Islets,” Three-Dimensional Aggregates of Allogeneic Islet and “Mesenchymal Stem Cells”

The authors demonstrated that the intraperitoneal administration of islet-sized “Neo-Islets”, generated by in vitro coaggregation of allogeneic, culture-expanded islet cells with high numbers of immuno-protective and cyto-protective mesenchymal stem cells, resulted in their omental engraftment in immune-competent, spontaneously diabetic nonobese diabetic mice. This achieved long-term glycemic control without immunosuppression and without hypoglycemia. [Stem Cells Transl Med] Full Article

PANCREATIC CANCER

Differential Expression of Aquaporin-3 and Aquaporin-5 in Pancreatic Ductal Adenocarcinoma

In pancreatic ductal adenocarcinomas samples aquaporin-5 (AQP5) was overexpressed in the apical membrane of intercalated and intralobular ductal cells while aquaporin-3 was expressed at the plasma membrane of ductal cells. AQP5 was also found in infiltrative cancer cells in duodenum. [J Surg Oncol] Abstract

LSL-Kras^G12D; LSL-Trp53^R172H/+; Ink4^flox/+; Ptf1/p48-Cre Mice Are an Applicable Model for Locally Invasive and Metastatic Pancreatic Cancer

The authors report a genetically engineered mouse model that harbors KRAS (Kras^G12D), TP53 (Trp53^R172H/+), CDKN2A (Ink4^flox/+) and Ptf1/p48-Cre (KPIC) mutations. Histopathology showed that KPIC mice developed adenocarcinoma that strongly resembled the pathology of human pancreatic cancer, characterized by rich desmoplastic stroma and low microvascularity. [PLoS One] Full Article

An Arduous Journey from Human Pluripotent Stem Cells to Functional Pancreatic β-Cells

The authors comprehensively summarize, compare and critically analyze intricacies of developing technologies, including differentiation platforms, robustness of protocols, and methodologies used to characterize human embryonic stem cells-derived β-like cells. They also discuss experimental issues that need to be resolved before these β-like cells can be used clinically. [Diabetes Obes Metab] Abstract

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

Real-World Evidence Shows Oral INVOKANA^® 300 mg Demonstrates Comparable A1C Reduction and Control to Injectable GLP-1 Receptor Agonists

Janssen Pharmaceuticals, Inc. announced real-world evidence showing people with type 2 diabetes initiated on oral INVOKANA^® (canagliflozin) 300 mg were as likely as matched patients initiated on injectable GLP-1 receptor agonists to achieve the recognized HEDIS standard of blood glucose control of A1C less than 8.0 percent. [Press release from Janssen Pharmaceuticals, Inc. (PR Newswire Association LLC.) discussing research presented at the American Association of Clinical Endocrinologists’ (AACE) 26^th Annual Scientific & Clinical Congress, Austin] Press Release

Poxel Announces Positive Top Line Results for Imeglimin Phase IIb Study in Japan for the Treatment of Type 2 Diabetes

POXEL SA announced positive top line Phase IIb data results for Imeglimin for the treatment of type 2 diabetes in Japan. The randomized, double-blind, placebo-controlled study of Imeglimin administered twice-daily for 24 weeks, demonstrated dose-dependent efficacy on two key measures of diabetes control in 299 Japanese patients. [POXEL SA] Press Release

Oramed Granted Canadian Patent for GLP-1 Analog Capsule

Oramed Pharmaceuticals Inc. announced that the Canadian Intellectual Property Office has granted Oramed a patent titled, “Methods and Compositions for Oral Administration of Exenatide”. The patent covers Oramed’s invention of an oral glucagon-like peptide-1 (GLP-1) analog. GLP-1 is an incretin hormone that stimulates the secretion of insulin from the pancreas. [Oramed Pharmaceuticals Inc. (PR Newswire Association LLC.)] Press Release

Mayo Clinic Endocrinologist Installed as President Elect of National Physician Organization

Daniel L. Hurley, MD, FACE, was installed as President-Elect of the American Association of Clinical Endocrinologists (AACE) at its 26^th Annual Scientific & Clinical Congress in Austin, Texas. [American Association of Clinical Endocrinologists] Press Release

Gregory R. Steinberg, PhD, Receives American Diabetes Association’s 2017 Outstanding Scientific Achievement Award

Gregory R. Steinberg, PhD, received the American Diabetes Association^® 2017 Outstanding Scientific Achievement Award. Dr. Steinberg will be recognized with this honor, given annually in recognition of research in diabetes that demonstrates particular independence of thought and originality, at the Association’s 77^th Scientific Sessions at the San Diego Convention Center. [American Diabetes Association^®] Press Release

Biotech Execs, Academic Leaders Make Case for NIH Funding at White House Meeting

Could the Trump administration be changing its mind about slashing funding for the National Institutes of Health (NIH)? Scientific leaders were optimistic after meeting at the White House with several biotech executives to discuss the “ecosystem” in which federally funded basic research leads to discoveries that companies turn into treatments. [ScienceInsider] Editorial

Scientists Relieved by Emmanuel Macron’s French Election Victory

French scientists say they’re relieved and happy that their country’s next president will be Emmanuel Macron, a 39-year-old former civil servant and economy minister who swept to victory in elections. Macron intends to make cuts to public spending, but has said he will ring-fence the budgets for research and higher education, areas that he wants to make the central plank of a program to boost innovation and cut unemployment. [Nature News] Editorial

Money Still Missing as the Plan to Synthesize a Human Genome Takes Another Step Forward

More than 200 biologists, businesspeople, and ethicists will converge upon the New York Genome Center in Manhattan to jumpstart what they hope will be biology’s next blockbuster: Genome Project-write, a still-unfunded sequel to the Human Genome Project where instead of reading a human genome, scientists create one from scratch and incorporate it into cells for various research and medical purposes. [ScienceInsider] Editorial

NEW The TGF-β Superfamily: Signaling in Development and Disease
July 9-14, 2017
Lisbon, Portugal

NEW 77^th American Diabetes Association Scientific Sessions
July 9-13, 2017
San Diego, California

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

NEW Assistant/ Associate Professor – Type 1 Diabetes Clinical and Basic Science (University of Colorado Anschutz Medical Campus)

Associate Principal Pathologist – Drug Safety & Metabolism (AstraZeneca)

Bioinformatician – Genomic Programming of Beta Cells (Imperial College London)

Postdoc Position – Cellular Modeling of Diabetes Risk Variants Using Pluripotent Stem Cells (University of California, San Diego)

Research Leaders – Career Development Award or Tenure Track (Medical Research Council)

Postdoctoral Fellow – Diabetes (University of Toronto)

Postdoctoral Associate – Pancreatic Beta Cells (Johns Hopkins School of Medicine)

Faculty Member – Endocrinology, Diabetes and Metabolism (Johns Hopkins University)

Professorship – Molecular Endocrinology (Ludwig-Maximilians-Universität München)

Cell Biology Scientist – Autoimmune Disease (Immunocore)

PhD Position – Biochemistry (Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences)

Postdoctoral Fellow – Diabetes Research (Child Health Institute of New Jersey)

Principle Investigator – Human Physiology and Experimental Medicine (University of Cambridge)

Postdoctoral Fellow – Prostate/Pancreatic Cancer (Medical College of Wisconsin)

Postdoctoral Positions – Life Sciences (Helmholtz Zentrum München)

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

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

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