Pancreatic Cell News Volume 8.14 | Apr 11 2017

TOP STORY

Virgin Beta Cells Persist throughout Life at a Neogenic Niche within Pancreatic Islets

Investigators discovered a population of immature beta cells that is present throughout life and forms from non-beta precursors at a specialized micro-environment or “neogenic niche” at the islet periphery. These cells express insulin, but lack other key beta cell markers, and are transcriptionally immature, incapable of sensing glucose, and unable to support calcium influx. [Cell Metab] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Targeting ABL-IRE1α Signaling Spares ER-Stressed Pancreatic β Cells to Reverse Autoimmune Diabetes

Researchers found that the ABL family of tyrosine kinases rheostatically enhances IRE1α’s enzymatic activities, thereby potentiating endoplasmic reticulum (ER) stress-induced apoptosis. During ER stress, cytosolic ABL kinases localize to the ER membrane, where they bind, scaffold, and hyperactivate IRE1α’s RNase. [Cell Metab] Abstract | Graphical Abstract

Efficient Generation of Glucose-Responsive Beta Cells from Isolated GP2⁺ Human Pancreatic Progenitors

The authors found that in vitro pancreatic endoderm cell (PEC) proliferation declines due to enhanced expression of the cyclin-dependent kinase (CDK) inhibitors CDKN1A and CDKN2A. However, they identified a time window when reducing CDKN1A or CDKN2A expression increased proliferation and yield of GP2⁺ PECs. [Cell Rep] Full Article | Graphical Abstract

Sphingosine Kinase 1-Interacting Protein Is a Novel Regulator of Glucose-Stimulated Insulin Secretion

Scientists found that sphingosine kinase 1-interacting protein (SKIP) is highly expressed in pancreatic β-cells but not in α-cells. An intraperitoneal glucose tolerance test showed that plasma glucose levels were decreased and insulin levels were increased in SKIP^−/− mice compared to SKIP^+/+ mice, but exendin-4-enhanced insulin secretion was masked. [Sci Rep] Full Article

Siglec-7 Restores β-Cell Function and Survival and Reduces Inflammation in Pancreatic Islets from Patients with Diabetes

Researchers report that certain sialic-acid-binding immunoglobulin-like-lectins (siglecs) are expressed in human pancreatic islets in a cell-type specific manner. Siglec-7 was expressed on β-cells and down-regulated in type 1 and type 2 diabetes and in infiltrating activated immune cells. [Sci Rep] Full Article

Effects and Underlying Mechanisms of Irisin on the Proliferation and Apoptosis of Pancreatic β Cells

Scientists investigated the effects and the potential underlying mechanisms of irisin on pancreatic β cell proliferation and apoptosis induced by high glucose. Both in vitro and in vivo experiments were conducted. [PLoS One] Full Article

PANCREATIC CANCER

Inhibition of Six1 Affects Tumor Invasion and the Expression of Cancer Stem Cell Markers in Pancreatic Cancer

Investigators showed that sine oculis 1 (Six1) is overexpressed in human pancreatic ductal adenocarcinoma and that its inhibition results in a decreased tumor progression in vitro and in vivo. [BMC Cancer] Full Article

Psoriasin Promotes Invasion, Aggregation and Survival of Pancreatic Cancer Cells; Association with Disease Progression

Psoriasin overexpression cell lines exhibited significantly increased growth and migration compared to control cells. In addition, psoriasin overexpression resulted in increased pancreatic cancer cell invasion which was associated with upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9. [Int J Oncol] Abstract

Curcumin and Its Cyclohexanone Analogue Inhibited Human Equilibrative Nucleoside Transporter 1 (ENT1) in Pancreatic Cancer Cells

Scientists determined whether curcumin and a related analogue, 2,6-bis((3-methoxy-4-hydroxyphenyl)methylene)-cyclohexanone (or A13), inhibited ENT1-mediated accumulation of [³H]uridine and [³H]gemcitabine into pancreatic cancer cells. They then confirmed the inhibition of gemcitabine accumulation by investigating whether curcumin/A13 could increase gemcitabine resistance in growth inhibition assays. [Eur J Pharmacol] Abstract | Graphical Abstract

Circulating Pancreatic Stellate (Stromal) Cells in Pancreatic Cancer—A Fertile Area for Novel Research

The authors explore the concept of circulating pancreatic stellate cells in pancreatic cancer and suggests future directions for research in this area. [Carcinogenesis] Abstract

Biology of Pancreatic Stellate Cells—More than Just Pancreatic Cancer

The authors review recent advances not only in the field of pancreatic stellate cell pathophysiology but also emphasize their roles in physiological processes. [Pflugers Arch] Full Article

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

Evotec Achieves First Milestone in Diabetes Alliance with Sanofi

Evotec AG announced that its strategic alliance with Sanofi in the field of diabetes has reached an important milestone, triggering a payment of EUR 3.0 million to Evotec, for achieving pre-clinical proof-of-concept. [Evotec AG] Press Release

PureTech Health Advances New Program Targeting Immunosuppressive Gamma Delta T Cells and Related Mechanisms

PureTech Health plc announced the launch of a new immuno-oncology program developing monoclonal antibodies to target newly discovered immunosuppressive mechanisms in pancreatic cancer and other solid tumors. [PureTech Health plc (Business Wire Inc.)] Press Release

Review of Canadian Science Calls for Better Oversight, Coordination — and More Money

To reinvigorate its science base, Canada needs to “reinvest” almost CAD$500 million in basic, investigator-led research over the next four years, according to a long-awaited review of the country’s science and innovation landscape. [ScienceInsider] Editorial

Critics Worry Faster FDA Drug Reviews Could Compromise Safety

For biotechs, waiting for new drugs to be approved is not as hard as it used to be. Since late last year, federal regulators have acted months earlier than expected to OK a bumper crop of new drugs from Massachusetts companies. The speedy decisions are welcomed by businesses that have made massive investments in developing experimental medicines and are eager for them to start generating revenue. But critics say the Food and Drug Administration (FDA)’s hurry-up mode may sacrifice patient safety — accelerating under pressure not only from the industry and investors, but from a regulation-averse Trump administration. [Boston Globe Media Partners, LLC] Editorial

U.S. Report Calls for Research Integrity Board

The U.S. research community needs to do a better job of both investigating misconduct allegations and promoting ethical conduct—or the government might act unilaterally in ways that scientists won’t like. That’s the implicit message sent by a new report out from the National Academies of Science, Engineering, and Medicine entitled Fostering Integrity in Research. [ScienceInsider] Editorial

NEW Regulation and Function of Small GTPases
June 11-16, 2017
West Palm Beach, United States

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NEW Cell Biology Scientist – Autoimmune Disease (Immunocore)

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

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)

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)

Principle Scientist – Translational Development (Celgene Corporation)

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

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