DIABETES & PANCREATITIS 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 PANCREATIC CANCER 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 |