Six week follow-up of metabolic effects induced by a high-fat diet and streptozotocin in a rodent model of type 2 diabetes mellitus

Abstract

This study was initiated to refine and characterize a nongenetic experimental model of type 2 diabetes mellitus and to follow up various metabolic parameters up to six weeks after diabetes induction. Male Wistar rats were divided into 4 groups: CON group--consumed standard rat chow and served as control; HFD group--consumed high-fat diet (45% calories as fat); STZ group-was injected once intraperitoneally with streptozotocin (35 mg/kg) on day 14, and DM-2 group--consumed high-fat diet and was injected with streptozotocin. The metabolic parameters were measured one week after streptozotocin injection (week 3) and at the end of the study (week 9). Our results confirm that HFD-group developed dyslipidaemia, obesity and insulin resistance. All metabolic parameters remained largely unaltered in STZ-group during the study. Only the combination of high-fat diet and streptozotocin (DM-2 group) induced type 2 diabetes that was characterized with moderate hyperglycaemia, insulin resistance, hypertriglyceridaemia, elevated free fatty acids, hypercholesterolaemia and increased plasma glucagon levels at the time of diabetes onset (week 3). The observed changes of the metabolic parameters after six additional weeks demonstrated an aggravated diabetic state, as confirmed from significantly increased fasting plasma glucose values, insufficient insulin secretion, severe hyperlipidaemia, increased glucagon levels, decreased serum adiponectin concentrations and significantly elevated urinary protein excretion. These results indicate that apart from its utility as a model of diabetes aetiology, this model could also be used for elucidating the role of the hormones adiponectin and glucagon in the progression of type 2 diabetes, as well as for investigating the diabetic complications.