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

Abstract

BackgroundPathophysiological 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.MethodAlbino 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.).ResultThe 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 NDF25 and NDF35 groups with 75.7% and 64.4% serum insulin respectively presented relative normoglycemia, whereas the FDF35 (85.8% serum insulin) were notably hyperglycaemia (>300 mg/dL) throughout the 6weeks post diabetes confirmation. These FDF35 rats were sensitive to glibenclamide, metformin and pioglitazone in lowering hyperglycaemia, hypertriglyceridemia and hypercholesterolemiaConclusionThe hyperglycaemia stability of the FDF35 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.

The Effects and Mechanism of Quercetin Dietary Supplementation in Streptozotocin-Induced Hyperglycemic Arbor Acre Broilers

“…STZ may increase the production of ROS and inhibit enzyme activities related with the scavenging of free radical [12]. Intraperitoneal administration of STZ (45-55 mg/kg body weight) decreased insulin sensitivity and induced hyperglycemia and diabetes mellitus in mice and rats [13,14]. At the same time, several studies have been conducted with natural antioxidants for the prevention of oxidative damage under high oxidative stress conditions.…”

Lansoprazole enhances the antidiabetic effect of dapagliflozin in fortified diet‐fed streptozotocin‐treated diabetic rats

“…As previously reported, type 2 diabetes (T2D) was successfully induced in animals by feeding them either a high‐fat diet (HFD) that resulted in glucose intolerance with impaired pancreatic function and hypercholesterolemia, [ 8 ] or a high‐fructose diet that induced hypertriglyceridemia and hyperinsulinemia. [ 9 ] In animal models using both diet regimens, the blood glucose levels of diabetic rats could not be reached and it failed the validation of antidiabetic drugs. [ 10 ] In addition, the IR of T2D could not be induced using low doses of streptozotocin (STZ).…”

“…This resulted in the model simulating the phenotype and the pathogenesis of human T2D. [9] Dapagliflozin (DAPA) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that was developed to treat T2D. [12] As DAPA is insulin-independent, any stage of T2D with severe IR or β-cell disfunction could be effectively treated using SGLT2 inhibitors.…”

The protective effects of Δ9-tetrahydrocannabinol against inflammation and oxidative stress in rat liver with fructose-induced hyperinsulinemia

“…It is reported that ROS have considered as one of the primary mediators in insulin resistance . Many studies reported that hyperinsulinemia is associated with diet and observed in fructose or high fat intake animal models of insulin resistance, metabolic syndrome and type 2 diabetes …”

“…[4] Many studies reported that hyperinsulinemia is associated with diet and observed in fructose or high fat intake animal models of insulin resistance, metabolic syndrome and type 2 diabetes. [5][6][7] Recently, the increase in the use of refined food, which is rich fructose, has raised concerns about the potential adverse on public health. The metabolic pathway of fructose is associated with hepatic gluconeogenesis and lipid biogenesis.…”