Pancreatic Cell News Volume 10.23 | Jun 18 2019

TOP STORY

Special Fibroblasts Help Pancreatic Cancer Cells Evade Immune Detection

Pancreatic ductal adenocarcinoma is characterized by an abundance of non-malignant stromal cells, and fibroblasts are one of the most common types of stromal cells. Researchers used single-cell RNA sequencing to classify the fibroblasts into three distinct sub-populations, identifying specific functions and characteristics unique to each. [Press release from Cold Spring Harbor Laboratory discussing online prepublication in Cancer Discovery] Press Release | Abstract | Full Article

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Intestinal Lysozyme Liberates Nod1 Ligands from Microbes to Direct Insulin Trafficking in Pancreatic Beta Cells

Scientists report that Nod1 ligands derived from intestinal bacteria acted as signal molecules and directly modulated insulin trafficking in pancreatic beta cells. The cytosolic peptidoglycan receptor Nod1 and its downstream adapter Rip2 were required for insulin trafficking in beta cells in a cell-autonomous manner. [Cell Res] Full Article

IAPP Toxicity Activates HIF1α/PFKFB3 Signaling Delaying β-Cell Loss at the Expense of β-Cell Function

Investigators established that human islet amyloid polypeptide (IAPP) misfolded protein stress activated HIF1α/PFKFB3 signaling, and this increased glycolysis disengaged from oxidative phosphorylation with mitochondrial fragmentation and perinuclear clustering, considered a protective posture against increased cytosolic Ca²⁺ characteristic of toxic oligomer stress. [Nat Commun] Full Article

Intra-Islet Ghrelin Signaling Does Not Regulate Insulin Secretion from Adult Mice

Exogenous ghrelin decreased insulin secretion in perifused isolated islets in a growth hormone secretagogue receptor (GHSR)-dependent manner. Islets isolated from mouse models lacking ghrelin or GHSR did not differ from controls in glucose-, alanine-, or GLP-1-stimulated insulin secretion during perifusion. [Diabetes] Abstract

The Pdx1 Bound Swi/Snf Chromatin Remodeling Complex Regulates Pancreatic Progenitor Cell Proliferation and Mature Islet β Cell Function

The authors demonstrated that mouse pancreas size and islet β cell function were controlled by the ATP-dependent Swi/Snf chromatin remodeling coregulatory complex that physically associated with Pdx1, a diabetes-linked transcription factor essential to pancreatic morphogenesis and adult islet-cell function and maintenance. [Diabetes] Abstract

A Versatile, Portable Intravital Microscopy Platform for Studying Beta-Cell Biology In Vivo

Researchers developed β-cell-selective virally-encoded fluorescent protein biosensors that could be rapidly and easily introduced into any mouse. They then coupled the use of these biosensors with intravital microscopy, a powerful tool that could be used to collect cellular and subcellular data from living tissues. [Sci Rep] Full Article

The Zinc Transporter Zip14 (SLC39a14) Affects Beta-Cell Function: Proteomics, Gene Expression, and Insulin Secretion Studies in INS-1E Cells

Scientists investigated the role of Zip14 in the INS-1E beta-cell line. Zip14 mRNA was upregulated during high glucose stimulation and Zip14 silencing led to increased intracellular insulin content. Furthermore, proliferation marker Mki67 was down-regulated in Zip14 siRNA-treated cells. [Sci Rep] Full Article

Quantitative Proteomics Reveals Novel Interaction Partners of Rac1 in Pancreatic β-Cells: Evidence for Increased Interaction with Rac1 under Hyperglycemic Conditions

Using co-immunoprecipitation and UPLC-ESI-MS/MS, investigators identified 324 Rac1 interaction partners in INS-1832/13 cells, which represented the largest Rac1 interactome to date. Furthermore, they identified 27 interaction partners that exhibited increased association with Rac1 in β-cells exposed to hyperglycemia. [Mol Cell Endocrinol] Abstract | Graphical Astract

MicroRNA-7 Directly Targets Reg1 in Pancreatic Cells

High levels of regenerating islet-derived protein 1 (Reg1) were noted by immunostaining and western blotting in acinar cells in contrast to islet cells. A reciprocal expression pattern was observed for miR-7. Overexpression of miR-7 resulted in Reg1 mRNA suppression and reduction of secreted Reg1 protein. [Am J Physiol Cell Physiol] Abstract

PANCREATIC CANCER

Multiplex Quantitative Analysis of Stroma-Mediated Cancer Cell Invasion, Matrix Remodeling, and Drug Response in a 3D Co-Culture Model of Pancreatic Tumor Spheroids and Stellate Cells

PANC-1 cells were cultured as tumor spheroids using previously developed minipillar chips, and co-cultured with pancreatic stellate cells (PSCs), both embedded in collagen gels. Effects of PSC co-culture on extracellular matrix fiber network, invasive migration of cancer cells, and expression of epithelial-mesenchymal transition-related proteins were examined. [J Exp Clin Cancer Res] Full Article

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Gluconeogenic Enzymes in β-Cells: Pharmacological Targets for Improving Insulin Secretion

Pancreatic β-cells express the gluconeogenic enzymes glucose 6-phosphatase, fructose 1,6-bisphosphatase, and phosphoenolpyruvate carboxykinase, which modulate glucose-stimulated insulin secretion through their ability to reverse otherwise irreversible glycolytic steps. The authors review current knowledge about the expression and regulation of these enzymes in the context of manipulating them to improve insulin secretion in diabetics. [Trends Endocrinol Metab] Abstract

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

Interim Results for Confirmatory Masitinib Study in Pancreatic Cancer with Pain

AB Science SA announced the positive recommendation of the Independent Data Monitoring Committee, following the interim analysis of study AB12005 in the firstline treatment of pancreatic cancer. [AB Science SA] Press Release

Japan Becomes the First Country to Approve Roche’s Personalized Medicine Rozlytrek

Roche announced that Japan’s Ministry of Health, Labour and Welfare has approved Rozlytrek^® for the treatment of adult and pediatric patients with neurotrophic tyrosine receptor kinase fusion-positive, advanced recurrent solid tumors. [F. Hoffmann-La Roche Ltd.] Press Release

Orgenesis Granted FDA Orphan Drug Designation for Autologous Insulin Producing Cells in the Treatment of Severe Hypoglycemia-Prone Diabetes Resulting from Total Pancreatectomy

Orgenesis Inc. announced that the FDA has granted Orphan Drug designation for its Autologous Insulin Producing cells as a cell replacement therapy for the treatment of severe hypoglycemia-prone diabetes resulting from total pancreatectomy due to chronic pancreatitis. [Orgenesis, Inc.] Press Release

UMN Medical School Researcher Awarded $100,000 Grant for Diabetes Research

University of Minnesota Medical School researcher Bernhard Hering, MD received a $100,000 grant from the Shakopee Mdewakanton Sioux Community to advance islet and kidney transplantation without the requirement of anti-rejection drugs. [University of Minnesota] Press Release

Trump Issues Executive Order that Could Reduce Scientific Advice

President Donald Trump issued an executive order on June 14 to cut back the number of advisory committees by at least a third by the end of September, according to a statement from the White House. The federal advisory committee system is the formal structure for government agencies to seek advice from experts including scientists. [The Scientist] Editorial

China Clamps Down on Foreign Use of Chinese Genetic Material and Data

China has announced new regulations for the use of human genetic resources that come from Chinese participants. The rules, announced on June 10, require international scientists using biomaterials from China to have a Chinese collaborator and go into effect on July 1. [The Scientist] Editorial

NEW 5^th Annual Cell & Gene Therapy Congress
October 29-30, 2019
London, United Kingdom

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

NEW Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

NEW Postdoctoral Fellow – Cancer Drug Response Research (University of Texas at Austin)

PhD Student – Diabetes (University of Edinburgh)

Postdoctoral Fellowship – Jak-Stat Signaling in Prostate and Pancreatic Cancer (Medical College of Wisconsin)

Scientist – Genetic and Genomic Epidemiology (International Agency for Research on Cancer)

Postdoctoral Position – Lung and Pancreatic Cancers (University of California, San Francisco)

Professor – Diabetes Research (University of Tennessee Health Science Center)

Postdoctoral Fellowship – Pancreatic Cancer (Oregon Health and Science University)

Postdoctoral Fellowship – Regenerative Medicine and Metabolic Biology (Indiana Biosciences Research Institute)

Research Positions – Pancreatic Beta-Cells (Université de Montréal)

Postdoctoral Fellow – Neuroscience and Diabetes (The Child Health Institute of New Jersey)

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