Islet adaptation to obesity and insulin resistance in WNIN/GR-Ob rats

• Published in: Islets Vol. 6; no. 5-6; p. e998099
• Main Authors: Singh, Himadri, Ganneru, Sireesha, Malakapalli, Venkata, Chalasani, Maniprabha, Nappanveettil, Giridharan, Bhonde, Ramesh R, Venkatesan, Vijayalakshmi
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-01-2014
• Subjects: Adaptation, Physiological - physiology; Age Factors; Animals; Body Weight; Female; Gene Expression - physiology; Glucagon - metabolism; hyperinsulinemia; hypertrophy; Insulin - metabolism; insulin resistance; Insulin Resistance - physiology; Insulin-Secreting Cells - pathology; Insulin-Secreting Cells - physiology; islets; Islets of Langerhans - cytology; Islets of Langerhans - pathology; Islets of Langerhans - physiopathology; Islets of Langerhans - ultrastructure; Microscopy, Electron, Scanning; Obesity - physiopathology; Organ Size; Oxidative Stress - physiology; Rats; Rats, Mutant Strains - physiology; Research Paper; Somatostatin - metabolism; WNIN/GR-Ob mutant rats; TNFα, tumor necrosis factors; hypertrophy; WNIN/GR-Ob mutant rats; T2D, type 2 diabetes; H&E, hematoxylin and eosin stain; NIN, National Institute of Nutrition; HOMA-IR, homeostatic model assessment for insulin resistance; FBG, fasting blood glucose; islets; IHC, immunohistochemistry; IGT, impaired glucose tolerance; NCLAS, National Center for Laboratory Animal Sciences; ROS, reactive oxygen species; insulin resistance; ANOVA, one-way analysis of variance; DAPI, 4′,6-diamidino-2-phenylindol; hyperinsulinemia; TBARS, thiobarbituric acid reactive substances; PBS, phosphate buffered saline; MS, metabolic syndrome; TEM, transmission electron microscopy; DTZ, Dithizone; WNIN, Wistar rats raised at National Institute of Nutrition; HI, hyperinsulinemia; KRBH, krebs ringer bicarbonate; SEM, scanning electron microscope; IR, insulin resistance; BM-MSCs, bone marrow derived mesenchymal stem cells
• ISSN: 1938-2014; 1938-2022
• DOI: 10.1080/19382014.2014.998099

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.