Volume 6.33 | Aug 25

Pancreatic Cell News 6.33 August 25, 2015
Pancreatic Cell News
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Researchers Uncover New Pathways for Diabetes Research
Researchers report that a key enzyme involved in the body’s response to glucose can essentially be corrupted by a new mechanism that scientists have not seen before. The enzyme is called glucokinase and serves as the body’s primary glucose sensor as it relays signals in the pancreas and liver telling other areas of the body to take up and process glucose. [Press release from Florida State University discussing online prepublication in the Proceedings of the National Academy of Sciences] Press Release | Abstract
Take the &quote;if&quote; out of &quote;diff&quote;: reduce variability when differentiating to definitive endoderm.
PUBLICATIONS (Ranked by impact factor of the journal)

Anti-CD3/Anti-CXCL10 Antibody Combination Therapy Induces a Persistent Remission of Type 1 Diabetes in Two Mouse Models
Anti-CD3 therapy of type 1 diabetes results in a temporary halt of the pathogenesis but does not constitute a permanent cure. The authors aimed at blocking such a re-entry by neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of diabetes and was superior to monotherapies with anti-CD3 or anti-CXCL10 alone. [Diabetes] Abstract

Activation of GLP-1 and Gastrin Signaling Induces In Vivo Reprogramming of Pancreatic Exocrine Cells into Beta Cells in Mice
Researchers tested the impact of glucagon-like peptide-1 receptor (GLP1R) expression on beta cell differentiation in vivo. Mice overexpressing GLP1R in pancreatic exocrine cells were generated by Cre-mediated recombination in sex-determining region Y-box 9-expressing cells and then treated with exendin-4 and/or gastrin. [Diabetologia] Abstract

Polyamine Biosynthesis Is Critical for Growth and Differentiation of the Pancreas
Investigators utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis. They identified that inhibition of polyamine biosynthesis reduces exocrine pancreas and β cell mass, and that these reductions are at the level of differentiation. [Sci Rep] Full Article

Inhibition of Stearoyl-CoA Desaturase 1 Impairs Palmitate-Derived Autophagy at the Step of Autophagosome-Lysosome Fusion in Pancreatic Beta-Cells
Scientists investigated whether stearoyl-CoA desaturase 1 (SCD1) activity is engaged in palmitate-induced pancreatic beta-cell autophagy. They found augmented apoptosis and diminished autophagy upon co-treatment of INS-1E cells with palmitate and an SCD1 inhibitor. [J Lipid Res] Abstract | Full Article

LXR-Mediated ABCA1 Expression and Function Are Modulated by High Glucose and PRMT2
Investigators proposed that changes in glucose levels modulate liver X receptor (LXR)-dependent gene expression. Using a mouse macrophage cell line and primary bone marrow derived macrophages cultured in normal or diabetes relevant high glucose conditions, they found that high glucose inhibits the LXR-dependent expression of ATP-binding cassette transporter A1 (ABCA1), but not ABCG1. [PLoS One]
Abstract | Press Release

PI3K Is Involved in P2Y Receptor-Regulated CAMP/Epac/Kv Channel Signaling Pathway in Pancreatic β Cells
In pancreatic β cells, activation of P2Y receptor (P2YR) has long been shown to stimulate insulin secretion in a glucose-dependent manner. Scientists used patch-clamp technique and insulin secretion assay to investigate the potential molecules that may link Epac to Kv channel inhibition induced by P2YR activation. [Biochem Biophys Res Commun] Full Article


Hyaluronic Acid Engineered Nano-Micelles Loaded with 3, 4-Difluorobenzylidene Curcumin for Targeted Killing of CD44+ Stem-Like Pancreatic Cancer Cells.
The anticancer activity of 3, 4-difluorobenzylidene curcumin loaded nano-micelles against MiaPaCa-2 and AsPC-1 human pancreatic cancer cells revealed dose-dependent cell killing. Results of cellular internalization further confirmed better uptake of hyaluronic acid engineered nano-micelles in triple-marker positive pancreatic cancer stem-like cells compared with triple-marker negative counterparts. [Biomacromolecules] Abstract

Transcriptomic Analysis of Pancreatic Cancer Cells in Response to Metformin and Aspirin: An Implication of Synergy
To gain further insight into their biological function in pancreatic cancer, researchers conducted a transcriptomic analysis using RNA sequencing to assess the differential gene expression induced by metformin and aspirin, alone or in combination, after treatment of PANC-1 cells for 48 hours. [Sci Rep] Full Article

The Plasma Membrane Calcium Pump in Pancreatic Cancer Cells Exhibiting the Warburg Effect Relies on Glycolytic ATP
Investigators explored whether this is a specific weakness of highly glycolytic plasma membrane Ca2+ ATPase (PMCA) by shifting PDAC cell metabolism from a highly glycolytic phenotype towards mitochondrial metabolism and assessing the effects of mitochondrial versus glycolytic inhibitors on ATP depletion, PMCA inhibition and intracellular Ca2+ concentration overload. [J Biol Chem] Abstract | Full Article

RNAi-Based Therapeutic Nanostrategy: IL-8 Gene Silencing in Pancreatic Cancer Cells Using Gold Nanorods Delivery Vehicles
Researchers demonstrated interleukin-8 (IL-8) gene silencing by employing an RNA interference (RNAi)-based gene therapy approach. This was achieved by using gold nanorods for efficient delivery of IL-8 small interfering RNA to the pancreatic cell lines of MiaPaCa-2 and Panc-1. [Nanotechnology] Abstract

Learn More: Standardized Tools for Cancer Research
The Skeleton in the Closet: Actin Cytoskeletal Remodeling in β-Cell Function
Perturbation of β-cell actin cytoskeleton remodeling could arise secondary to islet inflammation and fibrosis, possibly accounting in part for impaired β-cell function in type 2 diabetes. The authors review the role of actin remodeling in insulin secretion mechanisms and its close relationship with focal adhesions and myosin II. [Am J Physiol Endocrinol Metab] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
Jardiance® Demonstrated Cardiovascular (CV) Risk Reduction in People with Type 2 Diabetes at High Risk for CV Events
Boehringer Ingelheim and Eli Lilly and Company announced positive top-line results from EMPA-REG OUTCOME®. This is a long-term clinical trial investigating CV outcomes for Jardiance®/ (empagliflozin) in more than 7,000 adults with type 2 diabetes at high risk for CV events. [Eli Lilly and Company] Press Release

Intarcia Announces New Top-Line Phase III Results for Investigational Therapy ITCA 650 in Type 2 Diabetes: Freedom-2 Comparative Trial Demonstrates Superior & Sustained Glucose Control and Weight Reduction vs Januvia over 52 Weeks
Intarcia Therapeutics, Inc. announced positive top-line results from its 52-week Phase I FREEDOM-2 clinical trial to determine the comparative efficacy of the company’s late-stage investigational candidate ITCA 650 to Merck’s Januvia in reducing HbA1c in patients with type 2 diabetes following a year of treatment. [Intarcia Therapeutics, Inc.] Press Release

GACD Funds Landmark Research Into Prevention and Treatment of Type 2 Diabetes
Members of the Global Alliance for Chronic Diseases (GACD) will fund sixteen research projects to prevent and treat type 2 diabetes. The projects represent over $30 million of research funding over three to five years with a focus on implementation and intervention research in low- and middle-income countries, vulnerable populations in high-income countries and aboriginal communities. [Global Alliane for Chronic Diseases] Press Release

UMKC Awarded $1.4 Million for Diabetes Treatment Development
The University of Missouri-Kansas City (UMKC) School of Pharmacy has been awarded a $1.4 million grant from the National Institutes of Health for work on a new approach for artificial pancreas development to help the tens of millions of people who have diabetes. [University of Missouri-Kansas City] Press Release

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NEW Stem Cells: From Basic Biology to Disease Therapy
October 19-22, 2015
Suzhou, China

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW Postdoctoral Research Scientist – Pancreatic Cancer (Columbia University)

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

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Clinical Lecturer (University of Bristol)

Postdoctoral Position – Metabolic Diseases (ETH Zürich)

Postdoctoral Research Fellow – Development and Pathogenesis of Pancreatic Cancer (University College London)

Harry Eagle Scholar Awards for Postdoctoral Candidates (Albert Einstein College of Medicine of Yeshiva University)

Postdoctoral Positions – Cancer Research (Rutgers University)

Postdoctoral Fellowship – Pancreatic Beta Cell Biology and Regeneration, Relating to Diabetes (Mount Sinai School of Medicine)

Postdoctoral Fellowship – Immunopathogenesis of Type 1 Diabetes (Tongji Medical College)

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