Pancreatic Cell News Volume 8.36 | Sep 12 2017

TOP STORY

Inhibition of Y1 Receptor Signaling Improves Islet Transplant Outcome

Researchers demonstrated that Y1 receptor signaling inhibits insulin release in β-cells, and showed that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerated the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

DIABETES & PANCREATITIS

Gcg^CreERT2 Knockin Mice as a Tool for Genetic Manipulation in Pancreatic Alpha Cells

A Gcg^CreERT2 knockin mouse, which expresses a tamoxifen-inducible form of Cre from the endogenous preproglucagon (Gcg) gene locus, was generated by homologous recombination. The new Gcg^CreERT2 mouse line was crossed to the Rosa26^tdTomato Cre reporter mouse line in order to evaluate the tissue specificity, efficiency and tamoxifen dependency of Gcg^CreERT2-mediated recombination. [Diabetologia] Abstract

Transcriptomic and Functional Analyses on the Effects of Dioxin on Insulin Secretion of Pancreatic Islets and β-Cells

Through transcriptomic and ingenuity pathway analysis, scientists underlined that an ex-vivo TCDD treatment stimulated insulin-release in mouse pancreatic islets via the effect on the Akt-mTOR-p70S6K, AMPK and ERK1/2 pathways. Functional studies using both ex-vivo islets and the mouse β-cell-line validated the stimulatory effects of TCDD on basal-insulin secretion. [Environ Sci Technol] Abstract

Organotypic Pancreatoids with Native Mesenchyme Develop Insulin Producing Endocrine Cells

Investigators created three-dimensional organotypic pancreatic cultures, named pancreatoids, composed of embryonic day 10.5 murine epithelial progenitors and native mesenchyme. These progenitors assembled in scaffold-free, floating conditions and, with the inclusion of native mesenchyme, developed into pancreatoids expressing markers of different pancreatic lineages including endocrine-like cells. [Sci Rep] Full Article

Histone Deacetylase Regulates Insulin Signaling via Two Pathways in Pancreatic β Cells

The authors analyzed the epigenetic control of insulin receptor substrate 2 (IRS2) expression in the MIN6 mouse insulinoma cell line. They found concomitant IRS2 up-regulation and enhanced insulin signaling in MIN6 cells, which resulted in an increase in cell proliferation. [PLoS One] Full Article

An Ancestral Retroviral Protein Identified as a Therapeutic Target in Type-1 Diabetes

Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. In patients suffering from type 1 diabetes, HERV-W-Env protein was detected in 70% of sera, and its corresponding RNA was detected in 57% of peripheral blood mononuclear cells. [JCI Insight] Full Article

PANCREATIC CANCER

CDKN2B Deletion Is Essential for Pancreatic Cancer Development instead of Unmeaningful Co-Deletion due to Juxtaposition to CDKN2A

Investigators demonstrated that inactivation of Cdkn2b is necessary for induction of pancreatic cancer by oncogenic KRAS^G12D expression and inactivation of Tp53 and Cdkn2a in adult mouse pancreatic ductal cells. [Oncogene] Full Article

A Novel Inhibitory Anti-Invasive MAb Isolated Using Phenotypic Screening Highlights AnxA6 as a Functionally Relevant Target Protein in Pancreatic Cancer

The authors used a highly invasive clonal variant of the MDA-MB-435S cell line to generate monoclonal antibodies (MAbs), which were screened for anti-invasive activity against aggressive cancer cells in vitro. The molecular target of selected inhibitory MAb 9E1 was identified using immunoprecipitation/liquid chromatography-tandem mass spectrometry. The potential anti-tumor effects of MAb 9E1 were investigated in vitro together with immunohistochemical analysis of the 9E1 target antigen in normal and cancer tissues. [Br J Cancer] Abstract

Acceleration of Pancreatic Tumorigenesis under Immunosuppressive Microenvironment Induced by Reg3g Overexpression

Scientists evaluated Reg3g-regulated tumor immunity in tumor-implanted murine models, immune cells, and tumor microenvironment. In mice that had been orthotopically or ectopically implanted with Panc02 cells, Reg3g overexpression increased epidermal growth factor receptor and Ki67, diminished MHC-I and caspase-3 expression, and accelerated growth of tumors. [Cell Death Dis] Full Article

ATM-Deficiency Increases Genomic Instability and Metastatic Potential in a Mouse Model of Pancreatic Cancer

Researchers investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras. They showed that partial or total ATM deficiency cooperated with Kras^G12D to promote highly metastatic pancreatic cancer. [Sci Rep] Abstract

Adult-Onset Autoimmune Diabetes: Current Knowledge and Implications for Management

Scientists discuss the current understanding and gaps in knowledge regarding the pathophysiology and clinical features of adult-onset autoimmune diabetes and highlight the similarities and differences with classic type 1 diabetes mellitus and type 2 diabetes mellitus. [Nat Rev Endocrinol] Abstract

Pancreatic β Cell Regeneration as a Possible Therapy for Diabetes

The authors focus on endogenous regeneration, which can follow two pathways: enhanced replication of existing β cells and formation of new β cells from cells not expressing insulin, either by conversion from a differentiated cell type or differentiation from progenitors. [Cell Metab] Abstract

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

ARMO BioSciences’s Phase Ib Trials Demonstrate Continued Promising Response Rates and Survival in Patients with Advanced Pancreatic Cancer, NSCLC, and RCC

ARMO BioSciences, Inc. announced that clinical trial results on its lead investigational immuno-oncology drug AM0010 are being reported. These presentations will include additional clinical trial results from the ongoing Phase Ib studies of AM0010 in pancreatic cancer, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). [Press release from ARMO BioSciences, Inc. discussing research presented at the European Society of Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

ERYTECH Announces Positive Full Results from Phase IIb Study of Eryaspase in Combination with Chemotherapy for Treatment of Metastatic Pancreatic Cancer in Second-Line

ERYTECH Pharma announced the presentation of the full data from its Phase IIb study evaluating eryaspase in combination with chemotherapy for the treatment of metastatic pancreatic cancer. [Press release from ERYTECH Pharma discussing research presented at the European Society of Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

JDRF and vTv Therapeutics Announce Collaboration on Phase I Study of Novel Treatment for Type 1 Diabetes

vTv Therapeutics Inc. announced that JDRF will provide funding to support a Phase II Proof of Concept study to explore the effect of vTv Therapeutics’ liver-selective glucokinase activator TTP399 as an oral drug for the treatment of type 1 diabetes. [vTv Therapeutics Inc.] Press Release

International Award Honors UT Southwestern Scientist for Diabetes Research

Dr. Philipp Scherer, Director of the Touchstone Center for Diabetes Research at The University of Texas (UT) Southwestern, will receive the 2017 EASD-Novo Nordisk Foundation Diabetes Prize for Excellence in recognition of his research that explains the relationship between body fat and type 2 diabetes. [The University of Texas Southwestern] Press Release

Congress Rejects Trump Proposals to Cut Health Research Funds

Congress has not only rejected the president’s National Institutes of Health proposal; lawmakers from both parties have joined forces to increase spending on biomedical research — and have bragged about it. [The New York Times] Editorial

South Korean Researchers Lobby Government to Lift Human-Embryo Restrictions

More than a decade after a fraud scandal in stem-cell science rocked South Korea, scientists in the field are ramping up pressure on the government to relax the country’s strict regulations on human-embryo research — which many researchers label a ban. The nation’s bioethics committee held a public forum with the Ministry of Health and Welfare in Seoul, inviting 11 researchers and scholars to discuss possible changes to the country’s bioethics policies on research. [Nature News] Editorial

NEW Keystone Symposia: Vascular Biology and Human Diseases: From Molecular Pathways to Novel Therapeutics
February 25-March 1, 2018
Santa Fe, United States

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

NEW Postdoctoral Fellow – Diabetes (Harvard University)

Postdoctoral Research Fellow – RNA Metabolism in Pancreatic Cancer (Moffitt Cancer Center)

Postdoctoral Research Position – Pancreatitis and Pancreatic Cancer (Stanford University)

Postdoctoral Training Fellow – Systems and Precision Cancer Medicine (Institute of Cancer Research)

Faculty Position – Cancer Biology (The University of Texas Southwestern)

Postdoctoral Research Scientist – Tumor Environment (Cancer Research UK Beatson Institute)

Postdoctoral Position – Islet Biology (Sanofi)

Postdoctoral Scientist – hPSC Differentiation into Beta Cells (Helmholtz Zentrum München)

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)

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