title: Development of a diet-induced murine model of diabetes featuring cardinal metabolic and pathophysiological abnormalities of type 2 diabetes.
abstract: The persistent rise in global incidence of type 2 diabetes (T2D) continues to have significant public health and economic implications. The availability of relevant animal models of T2D is critical to elucidating the complexity of the pathogenic mechanisms underlying this disease and the implications this has on susceptibility to T2D complications. Whilst many high-fat diet-induced rodent models of obesity and diabetes exist, growing appreciation of the contribution of high glycaemic index diets on the development of hyperglycaemia and insulin resistance highlight the requirement for animal models that more closely represent global dietary patterns reflective of modern society. To that end, we sought to develop and validate a murine model of T2D based on consumption of an energy-dense diet containing moderate levels of fat and a high glycaemic index to better reflect the aetiopathogenesis of T2D. Male C57BL/6 mice were fed an energy-dense (ED) diet and the development of pathological features used in the clinical diagnosis of T2D was assessed over a 30-week period. Compared with control mice, 87% of mice fed an ED diet developed pathognomonic signs of T2D including glucose intolerance, hyperglycaemia, glycosylated haemoglobin (HbA1c) and glycosuria within 30 weeks. Furthermore, dyslipidaemia, chronic inflammation, alterations in circulating leucocytes and renal impairment were also evident in ED diet-fed mice compared with mice receiving standard rodent chow. Longitudinal profiling of metabolic and biochemical parameters provide support of an aetiologically and clinically relevant model of T2D that will serve as a valuable tool for mechanistic and therapeutic studies investigating the pathogenic complications of T2D.
authors.affiliation: Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia Jodie.Morris1@jcu.edu.au.
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Morris
authors.affiliation: Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Tahnee L
authors.initials: TL
authors.lastname: Bridson
authors.affiliation: Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Md Abdul
authors.initials: MA
authors.lastname: Alim
authors.affiliation: Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Rush
authors.affiliation: Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Rudd
authors.affiliation: Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Govan
authors.affiliation: Australian Institute of Tropical Health and Medicine, Division of Tropical Health and Medicine, James Cook University, Townsville, Queensland 4811, Australia.
authors.forename: Natkunam
authors.initials: N
authors.lastname: Ketheesan
keywords: Diet-induced; Glucose intolerance; Insulin resistance; Murine model; Type 2 diabetes