Pancreatic Cell News Volume 10.32 | Aug 20 2019

TOP STORY

Prevention and Reversion of Pancreatic Tumorigenesis through a Differentiation-Based Mechanism

Using a genetic mouse model that allowed for independent control of oncogenic Kras and Ptf1a expression, researchers demonstrated that sustained Ptf1a was sufficient to prevent Kras-driven tumorigenesis, even in the presence of tumor-promoting inflammation. Furthermore, reintroducing Ptf1a into established pancreatic intraepithelial neoplasia reverted them to quiescent acinar cells in vivo. Similarly, Ptf1a re-expression in human pancreatic cancer cells inhibited their growth and colony-forming ability. [Dev Cell] Abstract | Press Release

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

TrxG Complex Catalytic and Non-Catalytic Activity Play Distinct Roles in Pancreas Progenitor Specification and Differentiation

Pancreas progenitors were reallocated to the acinar lineage, primarily at the expense of NEUROG3⁺ endocrine progenitors. Later in development, acinar and endocrine cell numbers were decreased, and increased gene expression variance and reduced terminal marker activation in acinar cells led to their incomplete differentiation. [Cell Rep] Full Article | Graphical Abstract

Glucolipotoxicity Alters Insulin Secretion via Epigenetic Changes in Human Islets

Glucolipotoxic exposure impaired insulin secretion, increased apoptosis and significantly altered expression of 1,855 genes. These included 35 genes previously implicated in type 2 diabetes by GWAS e.g. TCF7L2 and CDKN2B. [Diabetes] Abstract

Mouse Pancreatic Ductal Organoid Culture as a Relevant Model to Study Exocrine Pancreatic Ion Secretion

Scientists used mouse pancreatic ductal fragments for experiments or were grown in Matrigel to obtain organoid cultures. Using PCR analysis they showed that gene expression of ion channels and transporters remarkably overlapped in primary ductal cells and organoids. [Lab Invest] Abstract

Protective Effect of Nobiletin on Isolated Human Islets Survival and Function against Hypoxia and Oxidative Stress-Induced Apoptosis

Researchers evaluated the effect of nobiletin on the cultured human islets. Isolated human islets were treated by different concentrations of nobiletin and cultured for 24 and 72 hours. Then, the islets viability, apoptosis, insulin and C-peptide secretion, and apoptosis markers were evaluated. [Sci Rep] Full Article

miRNAs Responsive to the Diabetic Microenvironment in the Human Beta Cell Line EndoC-βH1 May Target Genes in the FOXO, HIPPO and Lysine Degradation Pathways

The authors assessed changes in the miRNA milieu in response to high/low glucose, hypoxia, dyslipidemia and inflammatory factors in a humanized EndoC-βH1 beta cell culture system and performed miRPath analysis for each treatment individually. The ten miRNAs demonstrating the greatest dysregulation across treatments were then independently validated and gene set enrichment analysis to confirm targeted pathways undertaken. [Exp Cell Res] Abstract

PANCREATIC CANCER

Drp1 Promotes KRas-Driven Metabolic Changes to Drive Pancreatic Tumor Growth

The authors showed that dynamin-related protein 1 (Drp1) was required for KRas-driven anchorage-independent growth in fibroblasts and patient-derived pancreatic cancer cell lines, and it promoted glycolytic flux, in part through the regulation of hexokinase 2. Furthermore, Drp1 deletion imparted a significant survival advantage in a model of KRas-driven pancreatic cancer, and tumors exhibited a strong selective pressure against complete Drp1 deletion. [Cell Rep] Full Article | Graphical Abstract

Menin Coordinates C/EBPβ-Mediated TGFβ Signaling for Epithelial-Mesenchymal Transition and Growth Inhibition in Pancreatic Carcinogenesis

Investigators identified Menin as a promoter of epithelial-mesenchymal transition (EMT), which is largely associated with cell migration or metastasis, with a modest activity in cell growth inhibition. Ectopic expression of Menin suppressed the expression of CCAAT/enhancer-binding protein beta and epithelial-specific genes by histone deacetylation and further enhanced TGF signaling-related EMT process. [Mol Ther Nucleic Acids] Abstract

Truncated O-Glycans Promote Epithelial-to-Mesenchymal Transition and Stemness Properties of Pancreatic Cancer Cells

Scientists genetically deleted Core 1 synthase specific molecular chaperone in pancreatic ductal adenocarcinoma cells to express truncated O-glycans (SimpleCells, SC) which enhanced cell migration and invasion. Since epithelial-to-mesenchymal transition (EMT) played a vital role in metastasis, they have analyzed the induction of EMT in SC cells. Expressions of the mesenchymal markers were significantly high in SC cells as compared to WT cells. [J Cell Mol Med] Full Article

Hexokinase 2 Dimerization and Interaction with Voltage-Dependent Anion Channel Promoted Resistance to Cell Apoptosis Induced by Gemcitabine in Pancreatic Cancer

Hexokinase 2 (HK2) knockdown decreased pancreatic cancer cell proliferation, migration viability, and promoted cell apoptosis in vitro. HK2 high expression in pancreatic cancer showed GEM resistance. [Cancer Med] Abstract

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β Cell Dysfunction during Progression of Metabolic Syndrome to Type 2 Diabetes

Investigators focus on the current understanding from rodent and human studies of the progression of β cell responses during the development of metabolic syndrome, as well as recent findings addressing the complexity of β cell identity and heterogeneity within the islet during disease progression. [J Clin Invest] Abstract

VEGF-A and Blood Vessels: A Beta Cell Perspective

The authors summarize biology’s understanding of the role of vascular endothelial growth factor-A (VEGF-A) and endothelial cells in beta cell development, physiology and disease. In addition, the therapeutic potential of modulating VEGF-A levels in beta and beta-like cells for transplantation is discussed. [Diabetologia] Abstract

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

UC San Diego Receives $9 Million in Grants to Pinpoint Cellular Cause of Type 1 Diabetes

The University of California (UC) San Diego School of Medicine researchers have been awarded nearly $9 million to fund two multi-institutional research projects that use human pluripotent stem cells, CRISPR and human organoids to dissect beta cell defects and create a human cell model of type 1 diabetes aimed at identifying the elusive cellular actions leading to disease onset. [The University of California, San Diego] Press Release

Prevent Cancer Foundation^® Awards $250,000 in Community Grants

Through its community grants program, the Prevent Cancer Foundation^® will support ten projects focused on increasing cancer prevention and early detection in communities across the US, from Honolulu, Hawaii to Baltimore, Maryland. The projects were selected through a highly competitive grants process, and each program will receive a one-year, $25,000 grant. [Prevent Cancer Foundation^®] Press Release

Brazil’s Budget Cuts Threaten More Than 80,000 Science Scholarships

Brazil’s main science-funding agency will have to suspend more than 80,000 scholarships to postdoctoral researchers and graduate and undergraduate students starting in September unless it receives additional cash from the government. [Nature News] Editorial

The Push to Replace Journal Supplements with Repositories

Broken links, clunky formats, and outdated platforms have both authors and publishers turning to alternative solutions. [The Scientist] Editorial

NEW 2019 Diabetes Canada/CSEM Professional Conference
October 2-5, 2019
Winnipeg, Manitoba, Canada

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

NEW Research Technition – Diabetes, Allergies, and Lung Diseases (Helmholtz Zentrum München)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Auto-Immunity (Benaroya Research Institute)

Postdoctoral Researcher – Endocrinology, Diabetes, and Metabolism (The University of Alabama at Birmingham)

Research Scientist – Endocrine Pancreas Development (Helmholtz Zentrum München)

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

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

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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