WNIN/GR-Ob mutant rat is a novel animal model to study metabolic syndrome (obesity, insulin resistance, hyperinsulinemia, impaired glucose tolerance and cardiovascular diseases). We have investigated the islet characteristics of obese mutants at different age groups (1, 6 and 12 months) to assess the islet changes in response to early and chronic metabolic stress. Our data demonstrates altered islet cell morphology and function (hypertrophy, fibrotic lesions, vacuolation, decreased stimulation index, increased TNFα, ROS and TBARS levels) in mutants as compared to controls. Furthermore, network analysis (gene-gene interaction) studied in pancreas demonstrated increased inflammation as a key factor underlying obesity/metabolic syndrome in mutants. These observations pave way to explore this model to understand islet adaptation in response to metabolic syndrome.
Keywords: ANOVA, one-way analysis of variance; BM-MSCs, bone marrow derived mesenchymal stem cells; DAPI, 4′,6-diamidino-2-phenylindol; DTZ, Dithizone; FBG, fasting blood glucose; H&E, hematoxylin and eosin stain; HI, hyperinsulinemia; HOMA-IR, homeostatic model assessment for insulin resistance; IGT, impaired glucose tolerance; IHC, immunohistochemistry; IR, insulin resistance; KRBH, krebs ringer bicarbonate; MS, metabolic syndrome; NCLAS, National Center for Laboratory Animal Sciences; NIN, National Institute of Nutrition; PBS, phosphate buffered saline; ROS, reactive oxygen species; SEM, scanning electron microscope; T2D, type 2 diabetes; TBARS, thiobarbituric acid reactive substances; TEM, transmission electron microscopy; TNFα, tumor necrosis factors; WNIN, Wistar rats raised at National Institute of Nutrition; WNIN/GR-Ob mutant rats; hyperinsulinemia; hypertrophy; insulin resistance; islets.