Comparison of Indices of Insulin Resistance and Islet Beta-Cell Dysfunction across Rat Models of Diabetes Mellitus Induced By Modified Diets or Streptozotocin.

摘要

Background: Induction of insulin resistance in rodentsinvolves the use of Streptozotocin (STZ) or diets highin sucrose, fat or fructose; but the relative degrees ofinsulin resistance induced by each of these approachesare unclear. Aim and Objectives: We thereforecompared the degree to which intraperitoneal STZ withor without high-fat or high-fructose diet would induceinsulin resistance, glucose intolerance and islet β-celldysfunction in Wistar rats. Materials and Methods:Subsets of STZ-injected rats administeredstreptozotocin at 30 mg/kg body weight for fivesuccessive days were fed normal diet (STZ), or dietshigh in fat or fructose for 30 or 60 days.Normoglycaemic rats on normal rodent chow, High FatDiet (HFD) or High Fructose Drink (HFrD) constitutedthe Control (CTR), HFD or HFrD groups, respectively.Rats were anaesthetized and sacrificed at 30 or 60 daysof high fat or fructose feeding followed bymeasurement of fasting plasma glucose and insulin;and calculation of the HOMA-IR and HOMA-%β. OralGlucose Tolerance Test (OGTT) was done 48 hoursprior to killing the animals. Results: Glucose toleranceand islet β-cell function were most severely perturbedin the STZ-injected hyperglycaemic rats fed diets highin fructose or fat, as indicated by the significantlyincreased (p0.05) HOMA-IR or decreased HOMA-%β (p0.05) at 30 or 60 days compared with the CTR,STZ or diet-only groups. Weekly blood glucose wasmost markedly and significantly (p0.05) elevated inthese same (STZ+diet) groups, with impaired OGTT.Conclusion: The profound impairment of glucosetolerance and β-cell function in the STZ-inducedhyperglycaemic rats fed high-fat or high-fructose dietsupport the continued use of such models in thecharacterization of the molecular events associatedwith insulin resistance, and the testing of noveltherapeutic interventions.