Pancreatic Cell News Volume 9.12 | Mar 27 2018

TOP STORY

IL-22RA1/STAT3 Signaling Promotes Stemness and Tumorigenicity in Pancreatic Cancer

The authors found IL-22RA1 is highly but heterogeneously expressed in pancreatic cancer cells, with high expression associated with poor prognosis of pancreatic cancer patients. The IL-22RA1hi population from pancreatic tumor harbored higher stemness potential and tumorigenicity. [Cancer Res] Abstract

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DIABETES & PANCREATITIS

Adrenaline Stimulates Glucagon Secretion by Tpc2-Dependent Ca²⁺ Mobilization from Acidic Stores in Pancreatic α-Cells

Scientists examined the effects of adrenaline in mouse and human α-cells by a combination of electrophysiology, imaging of Ca²⁺ and PKA activity and hormone release measurements. They found that stimulation of glucagon secretion correlated with a PKA- and EPAC2-dependent elevation of [Ca²⁺]_i in α-cells, which occurred without stimulation of electrical activity, persisted in the absence of extracellular Ca²⁺ but was sensitive to ryanodine, bafilomycin and thapsigargin. [Diabetes] Abstract

Distinct Gene Expression Pathways in Islets from Individuals with Short‐ and Long‐Duration Type 1 Diabetes

The authors chose a human-focused method to investigate type 1 diabetes (T1D) disease mechanisms and potential targets for therapeutic intervention by directly analyzing human donor pancreatic islets from individuals with T1D. [Diabetes Obes Metab] Abstract

Bone Marrow‐Derived Mesenchymal Stem Cells Protect Islet Grafts against Endoplasmic Reticulum Stress‐Induced Apoptosis during the Early Stage after Transplantation

Investigators hypothesized that bone marrow‐derived mesenchymal stem cells (BMSCs) can protect grafted islets against endoplasmic reticulum stress‐induced apoptosis. In syngeneic streptozocin‐induced diabetic BALB/c mice, islet grafts decreased blood glucose levels; however, the effect was not fully functional from the immediate post‐transplant phase. [Stem Cells] Abstract

Loss of Deubiquitinase USP1 Blocks Pancreatic β-Cell Apoptosis by Inhibiting DNA Damage Response

Scientists identified the deubiquitinase ubiquitin-specific protease 1 (USP1) as an important player in the regulation of β-cell apoptosis under diabetic conditions. Genetic silencing and pharmacological suppression of USP1 blocked β-cell death in several experimental models of diabetes in vitro and ex vivo without compromising insulin content and secretion and without impairing β-cell maturation/identity genes in human islets. [iScience] Full Article | Graphical Abstract

PANCREATIC CANCER

Reduced Expression of the H19 Long Non-Coding RNA Inhibits Pancreatic Cancer Metastasis

H19 exhibited the second largest increase and represented the only non-protein coding gene among 11 genes identified that were elevated over 10-fold in lung-metastasis-derived pancreatic cancer cells compared with their parental cells using a mouse metastatic model. [Lab Invest] Abstract

Asparaginyl Endopeptidase Enhances Pancreatic Ductal Adenocarcinoma Cell Invasion in an Exosome-Dependent Manner and Correlates with Poor Prognosis

Scientists examined the putative functions of asparaginyl endopeptidase (AEP) in pancreatic carcinoma. Gain- and loss-of-function experiments demonstrated that knockdown of AEP expression significantly reduced the invasive ability of pancreatic cancer cells, whereas overexpression of AEP increased the invasive ability. [Int J Oncol] Abstract

Downregulation of miR-374b-5p Promotes Chemotherapeutic Resistance in Pancreatic Cancer by Upregulating Multiple Anti-Apoptotic Proteins

The decreased expression of miR-374-5p was associated with poor overall and progression-free survival in patients with pancreatic cancer. Furthermore, increased expression of miR-374b-5p abrogated, while the silencing miR-374b-5p increased the chemoresistance of pancreatic cancer cells to gemcitabine in vitro. [Int J Oncol] Abstract

New Understanding of β-Cell Heterogeneity and In Situ Islet Function

The authors discuss recent findings revealing functional β-cell subpopulations in the intact islet, the underlying basis for these identified subpopulations, and how these subpopulations may influence in situ islet function. [Diabetes] Full Article

Impact of RUNX2 on Drug-Resistant Human Pancreatic Cancer Cells with p53 Mutations

Accumulating evidence strongly suggests that p53 mutations contribute to the acquisition and/or maintenance of drug-resistant property of pancreatic cancer. Scientists discuss how to overcome the serious drug-resistant phenotype of pancreatic cancer. [BMC Cancer] Full Article

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Scientists Launch Global Effort to Find the Next Diabetes Drug

University of Southern California researchers have launched a massive scientific effort to construct a detailed, virtual 3D model of the pancreatic beta cell and its components — a global project that aims to one day curb the worldwide rise of diabetes. [University of Southern California] Press Release

vTv Therapeutics Announces Completion of Phase Ib Study Evaluating TTP399 for the Treatment of Type 1 Diabetes

vTv Therapeutics Inc. announced the completion of Phase Ib of Simplici-T1, an adaptive Phase Ib/II study assessing the pharmacokinetics, pharmacodynamics, safety and tolerability of TTP399 in adult patients with type 1 diabetes. [vTv Therapeutics Inc.] Press Release

Cambridge Analytica Controversy Must Spur Researchers to Update Data Ethics

Revelations keep emerging in the Cambridge Analytica personal-data scandal, which has captured global public attention. But when the dust settles, researchers harvesting data online will face greater scrutiny. And so they should. [Nature News] Editorial

Duke’s Mishandling of Misconduct Prompts New U.S. Government Grant Oversight

The U.S. National Institutes of Health imposed unusual new requirements on researchers based at Duke University in Durham, North Carolina, who receive federal funds. The changes are a response to concerns over how the institution handled recent cases involving research misconduct and grant management. [ScienceInsider] Editorial

Massive Cyberhack by Iran Allegedly Stole Research from 320 Universities, Governments, and Companies

Nine Iranians working on behalf of the Islamic Revolutionary Guard Corps hacked the computers of 7998 professors at 320 universities around the world over the past five years, an indictment filed by a federal grand jury alleges. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Cell Death
August 5-10, 2018
Newry, Maine, United States

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

NEW Postdoctoral Scholar – Cancer (University of California, San Francisco)

NEW Postdoctoral Position – Protein Biochemistry (Vlaams Instituut voor Biotechnologie)

Postdoctoral Researcher – Diabetes-Induced Osteopathy (NUI Galway)

Postdoctoal Fellow – Pancreatic Cell (Inserm)

Postdoctoral Fellow – Diabetes and Pancreatic Islet Biology (Vanderbilt University)

Postdoctoral Scientist – Epigenetic Mechanisms (Geneva University)

Postdoctoral Fellow – Epigenetic Regulation of Pancreatic Beta-Cell Mass (City of Hope)

Postdoctoral Positions – Pancreatic Cancer Cells (Fox Chase Cancer Center)

Postdoctoral Research Fellow – Diabetes (University of Chicago)

Postdoctoral Fellow – Diabetes Research (Joslin Diabetes Center)

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