Volume 7.12 | Mar 29

Pancreatic Cell News 7.12 March 29, 2016
Pancreatic Cell News
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Presence of Hormone at Key Developmental Period May Point to Origin of Type 2 Diabetes in Kids
A new study reports that the presence of leptin – a hormone secreted by fat cells that is critical to maintaining energy balance in the body – inhibits the prenatal development of neuronal connections between the brain and pancreas. The findings could help explain the origin of type 2 diabetes, particularly in children of obese mothers. [Press release from The Saban Research Institute of Children’s Hospital Los Angeles discussing online prepublication in Cell Reports] Press Release | Full Article | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)

Sodium Intake Regulates Glucose Homeostasis through the PPARδ/Adiponectin-Mediated SGLT2 Pathway
Scientists report that high sodium intake remarkably increased natriuresis in wild-type mice, but this effect was blunted in adipose-specific PPARδ knockout mice and diabetic mice. [Cell Metab] Abstract | Graphical Abstract

IgG4+ B-Cell Receptor Clones Distinguish IgG4-Related Disease from Primary Sclerosing Cholangitis and Biliary/Pancreatic Malignancies
Scientists demonstrated that dominant IgG4+ B-cell receptor clones determined by next-generation sequencing accurately distinguish patients with IgG4-associated cholangitis/autoimmune pancreatitis from those with primary sclerosing cholangitis and biliary/pancreatic malignancies. [Hepatology] Abstract

Metformin Stimulates IGFBP-2 Gene Expression through PPARalpha in Diabetic States
Researchers demonstrated that metformin upregulates insulin-like growth factor-binding protein 2 (BP-2) expression through the AMPK-Sirt1-PPARα cascade pathway. [Sci Rep] Full Article

Silicon Nanopore Membrane (SNM) for Islet Encapsulation and Immunoisolation under Convective Transport
Scientists report the development and characterization of a new generation of semipermeable ultrafiltration membrane, the silicon nanopore membrane, designed with approximately 7 nm-wide slit-pores to provide middle molecule selectivity by limiting passage of pro-inflammatory cytokines. [Sci Rep] Full Article

Increased Oxidative Stress and Apoptosis in the Hypothalamus of Diabetic Male Mice in the Insulin Receptor Substrate-2 Knockout Model
The authors analyzed whether the diabetes associated with the absence of insulin receptor substrate-2 (IRS2) results in hypothalamic injury and the intracellular mechanisms involved. Only diabetic IRS2-/- mice showed increased cell death and activation of caspases -8 and -3 in the hypothalamus. [Dis Model Mech] Full Article

Functional Langerinhigh-Expressing Langerhans-Like Cells Can Arise from CD14highCD16 Human Blood Monocytes in Serum-Free Condition
The authors sought to characterize key factors that induce differentiation of langerinhigh-expressing monocyte-derived Langerhans-like cells. They identified GM-CSF and TGF-β1 as key cytokines to generate langerinhigh-expressing cells but only in serum-free conditions. [J Immunol] Abstract

β-Adrenergic Receptor Agonist, Compound 49b, Inhibits TLR4 Signaling Pathway in Diabetic Retina
The authors hypothesized that diabetes would increase Toll-like receptor 4 (TLR4) signaling, which could be inhibited by a β-adrenergic receptor agonist (Compound 49b) previously shown to have anti-inflammatory actions. [Immunol Cell Biol] Abstract

Obesity-Induced DNA Released from Adipocytes Stimulates Chronic Adipose Tissue Inflammation and Insulin Resistance
The authors showed that obesity-related adipocyte degeneration causes release of cell-free DNA, which promotes macrophage accumulation in adipose tissue via Toll-like receptor 9, originally known as a sensor of exogenous DNA fragments. [Sci Adv] Full Article


Pharmacological Macrophage Inhibition Decreases Metastasis Formation in a Genetic Model of Pancreatic Cancer
Researchers studied the impact of pharmacological macrophage depletion by liposomal clodronate in a genetic mouse model of pancreatic cancer. [Gut] Abstract

Suppression of Pancreatic Cancer Growth and Metastasis by HMP19 Identified through Genome-Wide shRNA Screen
To identify genes suppressing metastasis, a genome-wide shRNA screen was done using the human non-metastatic pancreatic ductal adenocarcinoma cell line, S2-028. After identification of candidates, functional validation was done using intrasplenic and orthotopic injections in athymic mice. [Int J Cancer] Abstract

KRAS G12D Mutation Subtype Is a Prognostic Factor for Advanced Pancreatic Adenocarcinoma
The exon-2 KRAS mutation status was tested on endoscopic ultrasound-guided fine-needle aspiration biopsy material of patients with proven locally advanced and/or metastatic pancreatic ductal carcinoma. [Clin Transl Gastroenterol] Full Article

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Viral Infections in Type 1 Diabetes Mellitus — Why the β Cells?
Some data indicate that pancreatic islet α cells trigger a more efficient antiviral response to infection with diabetogenic viruses than do β cells, and so are able to eradicate viral infections without undergoing apoptosis. This difference could account for the varying ability of islet-cell subtypes to clear viral infections and explain why chronically infected pancreatic β cells, but not α cells, are targeted by an autoimmune response and killed during the development of type 1 diabetes mellitus. [Nat Rev Endocrinol] Abstract

Visit our reviews page to see a complete list of reviews in the pancreatic cell research field.
GlycoMimetics to Present New Preclinical Data on Its E-Selectin-CXCR4 Dual Antagonist
GlycoMimetics, Inc. announced that pre-clinical research demonstrating the potential of its third drug candidate, GMI-1359, will be presented. An oral presentation and a poster will highlight data on GMI-1359, a potent dual antagonist of both E-selectin and CXCR4, demonstrating anti-tumor activity in preclinical models of pancreatic cancer and acute myeloid leukemia, respectively. [Press release from GlycoMimetics, Inc. discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2016, New Orleans] Press Release

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Merrimack Announces Inclusion of ONIVYDE® (Irinotecan Liposome Injection) as a Category 1 Treatment Option in the 2016 NCCN Guidelines for Pancreatic Adenocarcinoma
Merrimack Pharmaceuticals, Inc. announced the National Comprehensive Cancer Network (NCCN) has included ONIVYDE® (irinotecan liposome injection) in combination with fluorouracil and leucovorin in its 2016 Clinical Practice Guidelines in Oncology for pancreatic adenocarcinoma. [Merrimack Pharmaceuticals, Inc.] Press Release

Chi-Med Initiates Sulfatinib Phase III Registration Study in Pancreatic Neuroendocrine Tumor Patients
Hutchison China MediTech Limited announces that Hutchison MediPharma Limited, its drug R&D subsidiary, has initiated SANET-p, a Phase III registration trial of sulfatinib in China in patients with pancreatic neuroendocrine tumors. [Hutchison China MediTech Limited] Press Release

Poxel Has been Granted U.S. Composition of Matter Patent for Direct AMPK Activator PXL770 for the Potential Treatment of Type 2 Diabetes and Related Disorders
Poxel SA announced that the U.S. Patent and Trademark Office has granted the patent (US patent number US-9,284,329) filed by Poxel covering direct AMPK activators. [Poxel SA] Press Release
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW International Agency for Research on Cancer (IARC) 50th Anniversary Conference
July 7-10, 2016
Lyon, France

Visit our events page to see a complete list of events in the pancreatic cell community.
NEW Postdoctoral Fellow – Diabetes Induced Neural Tube Defects (UMB School of Medicine)

NEW Postdoctoral Fellow – Pancrease Preconditioning (Centre Européen d’Etude du Diabète)

NEW Postdoctoral Fellow – Pancreatic Zinc Transporter as Therapeutic Target (Johns Hopkins School of Medicine)

Research Scientist – Various Fields (King Abdullah International Medical Research Center)

Postdoctoral Fellowship – Pancreatic Cancer (Fred Hutchinson Cancer Research Center)

Master Studentship – Exercise and Diabetes (Swansea University)

Part Time Researcher – Diabetes (University of Bergen)

Postdoctoral Research Fellowship – Pancreatic Cancer Biology (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellowship – Surgical Oncology in Pancreatic Cancer (University of Nebraska Medical Center)

Postdoctoral Research Fellowship – Pancreatic Progenitors in Development (Johns Hopkins University Institute of Genetic Medicine)

Postdoctoral Fellowship – Metabolism and Cancer (Monash University)

Postdoctoral Fellowship – Mechanisms of Atherosclerosis, Diabetes and Obesity (Washington University School of Medicine)

Assistant Professor of Surgery – Molecular Biology and Pancreatic Development (University of Pittsburgh)

Postdoctoral Fellowship – Neural Mechanisms of Diabetes (Albert Einstein College of Medicine)

Faculty Position – Metabolic Disease Research (Lewis Katz School of Medicine)

MD/PhD Researcher – Biomedical Sciences (Hannover Medical School)

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