Pancreatic Cell News Volume 8.32 | Aug 15 2017

TOP STORY

Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport

To identify new metabolic regulators of pancreatic ductal adenocarcinoma (PDAC) tumor growth and metastasis, researchers systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. They found that p53 transcriptionally represses paraoxonase 2, which regulates GLUT1-mediated glucose transport via stomatin. [Mol Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Mitigating Ischemic Injury of Stem Cell-Derived Insulin-Producing Cells after Transplant

Scientists showed that more than half of stem cell-derived insulin-producing cells (SCIPCs) die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPCs in vitro. Amino acid supplementation rescued SCIPCs from nutrient deprivation, likely by providing cellular energy. [Stem Cell Reports] Full Article | Graphical Abstract

Glucose Potentiates β-Cell Function by Inducing Tph1 Expression in Rat Islets

Global gene expression patterns revealed that tryptophan hydroxylase 1 (Tph1) was the most profound of genes that are up-regulated in rat islets exposed to high glucose. Calcium and cAMP signals synergistically mediated glucose-stimulated Tph1 transcription in β-cells by activating cAMP-responsive element–binding protein and promoting its binding with a Tph1 promoter. [FASEB J] Abstract

Differential Effects of Linagliptin on the Function of Human Islets Isolated from Non-Diabetic and Diabetic Donors

Researchers employed human islets isolated from donors with and without type 2 diabetes (T2D) and evaluated how they responded to linagliptin treatment. Their data showed that linagliptin significantly improved glucose-stimulated insulin secretion for both non-diabetic and diabetic human islets, but its effectiveness on T2D islets was lower than on normal islets. [Sci Rep] Full Article

Long Noncoding RNAs Are Dynamically Regulated during β-Cell Mass Expansion in Mouse Pregnancy and Control β-Cell Proliferation In Vitro

Investigators tested the hypothesis that long noncoding RNAs (lncRNAs) regulate β-cell proliferation in response to prolactin in the context of β-cell mass compensation in pregnancy. They found that a group of lncRNAs was differentially regulated in mouse islets at 14.5 days of pregnancy. [PLoS One] Full Article

Effect of Intrapancreatic Fat on Diabetes Outcomes after Total Pancreatectomy with Islet Autotransplantation

Researchers tested whether pancreatic fatty infiltration has a negative effect on metabolic outcomes following total pancreatectomy with islet autotransplantation. Patients with high pancreatic fat were more likely to be insulin dependent, with higher post-prandial glucose excursion. [J Diabetes] Abstract

Insulin-Producing Cells Derived from ‘Induced Pluripotent Stem Cells’ of Patients with Fulminant Type 1 Diabetes: Vulnerability to Cytokine Insults and Increased Expression of Apoptosis-Related Genes

Scientists generated induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes and evaluated the cytokine-induced apoptotic reactions of beta-like insulin-producing cells differentiated from the iPSCs. [J Diabetes Investig] Abstract

PANCREATIC CANCER

Inhibition of Hypoxic Response Decreases Stemness and Reduces Tumorigenic Signaling Due to Impaired Assembly of HIF1 Transcription Complex in Pancreatic Cancer

Investigators evaluated the effect of Minnelide on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer. Their results showed that upon treatment with triptolide, HIF-1α protein accumulated in pancreatic cancer cells even though hypoxic response was decreased in them. [Sci Rep] Full Article

The Inhibitory Effect of 5,7-DMF on Pancreatic Sphere-Forming Cell Function Mediated by FoxM1 Gene Expression

Scientists isolated the pancreatic sphere-forming cells from pancreatic cancer cell line PANC-1 by sphere-forming method and found that the sphere-forming ability and cell migration rate of pancreatic sphere-forming cells were significantly inhibited by 5,7-DMF treatment, which was supported by the corresponding changes of several EMT biomarkers after being treated with 5,7-DMF. [J Cell Biochem] Abstract

New Insights into Non-Conventional Epitopes as T Cell Targets: The Missing Link for Breaking Immune Tolerance in Autoimmune Disease?

Researchers discuss the current understanding of mechanisms through which non-conventional epitopes may be generated, focusing on several recently described pathways that can transpose germline-encoded sequences. They contextualize these discoveries around type 1 diabetes, the prototypic organ-specific autoimmune disease in which specific HLA-DQ molecules confer high risk. [J Autoimmun] Abstract

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Metacrine Announces Collaboration on Development of FGF1 Variants for Glucose Lowering and Improving Insulin Sensitivity

Metacrine, Inc. announced it has entered a collaboration with Novo Nordisk A/S to develop fibroblast growth factor 1 variants for glucose lowering and insulin sensitization. [Metacrine, Inc.] Press Release

CARsgen Launches First-in-Class Anti-Claudin18.2 CAR-T Clinical Trial

CARsgen Therapeutics announced its first-in-class anti-Claudin18.2-CAR-T cell therapy for gastric and pancreatic cancers has entered into Phase I clinical trial and starts patients recruitment at Changhai Hospital of Shanghai. [CARsgen Therapeutics (PR Newswire Association LLC.)] Press Release

New FDA Security Rules Will Bar Agency from Hiring Some Foreign Nationals

The FDA is moving to adopt a new policy on security background checks that is sowing confusion and alarm among some of its scientists. The change, described in a “communications plan” shared with the agency’s senior staff, appears to effectively bar the agency from hiring—as employees or contractors—foreign nationals who have not lived in the United States for a total of three out of the last five years. [ScienceInsider] Editorial

Researchers Rally around Science Advocate Convicted in Egypt

Scientists, engineers, and others are hoping an Egyptian court will reconsider a prison sentence given to one of the nation’s most prominent science advocates. An Egyptian judge sentenced Ismail Serageldin, founding director of Egypt’s Library of Alexandria, to 3.5 years in prison for financial misdemeanors. [Science Insider] Editorial

Budget Cuts Fuel Frustration among Japan’s Academics

Japan’s premier scientific research institution, RIKEN, turned 100 this year, and celebrated with a grand ceremony attended by the empress and emperor. But not everybody was in the mood to party. In the old days, RIKEN was known as a paradise for scientists because of its generous funding. No longer: as Japan cuts off funds in the face of continuing financial uncertainty, the cracks are starting to show. [Nature News] Editorial

Americans Are Becoming More Open to Human Genome Editing, Survey Finds, but Concerns Remain

Earlier surveys of Americans found a reluctance to support human genome editing, with many respondents expressing ethical and other concerns about such intentional tinkering. A new survey found that two-thirds of the 1600 respondents thought genome editing was generally “acceptable.” But that acceptance was qualified, and colored by religious beliefs and scientific knowledge. [ScienceInsider] Editorial

NEW EACR-MRS: Seed and Soil: In Vivo Models of Metastasis
November 27-29, 2017
Berlin, Germany

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NEW Postdoctoral Fellow – Pancreatic Cancer (Fred Hutchinson Cancer Research Center)

NEW Scientist – Diabetes and Obesity (Helmholtz Zentrum München)

Assistant Investigator – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute)

Postdoctoral Fellow – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute)

Research Assistant – Cancer Genetics, Epigenetics and Biomarkers (Baylor Research Institute)

Postdoctoral Scholar – Pancreatic and Lung Cancer Research (University of California, San Francisco)

Postdoctoral Position – Immunology (Harvard Medical School)

Faculty Positions – Diabetes, Obesity, and Metabolism (University of Pittsburgh)

Postdoctoral Research Position – Pancreatic Cancer Metabolism (Eppley Institute for Research in Cancer)

Postdoctoral Research Scientist – Mechanisms of Obesity and Diabetes (NYU Langone Medical Center)

Postdoctoral Researcher – Obesity and Diabetes (University of Iowa)

Assistant Professor – Metabolic Disorders (Umeå University)

Group Leader – Cancer Research (University of Lille)

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