Appropriate Insulin Level in Selecting Fortified Diet-Fed, Streptozotocin-Treated Rat Model of Type 2 Diabetes for Anti-Diabetic Studies

BACKGROUND: Pathophysiological investigation of disease in a suitable animal model is a classical approach towards development of a credible therapeutic strategy. This study examined appropriate insulin level in selecting animal model for type 2 diabetes (T2D) studies. METHOD: Albino Wistar rats (150-200g) were divided into two groups fed with commercially available normal-diet-feed (NDF) and water or fortified diet feed (FDF) (10g NDF per gram of margarine) with 20% fructose solution as drinking water. After 6 weeks of dietary regimen both groups were divided into 5 sub-groups and injected intraperitoneally with a graded dose of streptozotocin (STZ) (0, 25, 35, 45 & 55mg/kg bw.). RESULT: The result showed that the FDF-fed rats increased significantly in body weight, basal serum insulin, total cholesterol, triglycerides and blood glucose levels as compared to NDF-fed rats. Ten days post STZ induction, the groups treated with STZ (45 & 55 mg/kg) developed frank hyperglycaemia with < 46.8% serum insulin, a severe deficiency typical of diabetes type 1. The NDF(25) and NDF(35) groups with 75.7% and 64.4% serum insulin respectively presented relative normoglycemia, whereas the FDF(35) (85.8% serum insulin) were notably hyperglycaemia (>300 mg/dL) throughout the 6weeks post diabetes confirmation. These FDF(35) rats were sensitive to glibenclamide, metformin and pioglitazone in lowering hyperglycaemia, hypertriglyceridemia and hypercholesterolemia CONCLUSION: The hyperglycaemia stability of the FDF(35) rats (85.5% insulin) together with their sensitivity to 3 different hypoglycaemic drugs strongly suggests their suitability as a non-genetic model of T2D. Hence the study shows that circulating serum insulin ≥ 85.8% with overt hyperglycaemia may be utilized as the benchmark in selecting rat models for T2D studies.