ABSTRACT
Background: Prediabetes is a condition of intermediate hyperglycemia that may progress to type 2 diabetes. Vitamin D deficiency has been frequently linked to insulin resistance and diabetes. The study aimed to investigate the role of D supplementation and its possible mechanism of action on insulin resistance in prediabetic rats. Method: The study was conducted on 24 male Wistar rats that were randomly divided into 6 rats as healthy controls and 18 prediabetic rats. Prediabetic rats were induced with a high-fat and high-glucose diet (HFD-G) combined with a low dose of streptozotocin. Rats with the prediabetic condition were then randomized into three groups of 12-week treatment: one group that received no treatment, one that received vitamin D3 at 100 IU/kg BW, and one group that received vitamin D3 at 1000 IU/kg BW. The high-fat and high-glucose diets were continuously given throughout the twelve weeks of treatment. At the end of the supplementation period, glucose control parameters, inflammatory markers, and the expressions of IRS1, PPARγ, NF-κB, and IRS1 were measured. Results: Vitamin D3 dose-dependently improves glucose control parameters, as shown by the reduction of fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated albumin, insulin levels, and markers of insulin resistance (HOMA-IR). Upon histological analysis, vitamin D supplementation resulted in a reduction of the islet of Langerhans degeneration. Vitamin D also enhanced the ratio of IL-6/IL-10, reduced IRS1 phosphorylation at Ser307, increased expression of PPAR gamma, and reduced phosphorylation of NF-KB p65 at Ser536. Conclusion: Vitamin D supplementation reduces insulin resistance in prediabetic rats. The reduction might be due to the effects of vitamin D on IRS, PPARγ, and NF-κB expression.
Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Prediabetic State , Rats , Male , Animals , Prediabetic State/drug therapy , Prediabetic State/metabolism , NF-kappa B , PPAR gamma , Diabetes Mellitus, Type 2/metabolism , Blood Glucose/analysis , Dietary Supplements/analysis , Rats, Wistar , Vitamin D , Vitamins/pharmacology , Vitamins/therapeutic use , Cholecalciferol/pharmacologyABSTRACT
AIM AND OBJECTIVE: The present study aims to investigate whether the antihyperglycemic effect of Murraya koenigii is mediated by antioxidant properties and insulin mimetic effect. METHODS: Thirty Spraque-Dawley rats were induced hyperglycemia by streptozotocin and nicotinamide (STZ-NA). The STZ-NA diabetic rats were treated with an ethanolic extract of Murraya koenigii 200 mg/kg b.w and 400 mg/kg b.w. One group was treated with glibenclamide (1 mg/kg b.w). After the administration of Murraya koenigii extract and glibenclamide for four weeks, the rats were sacrificed. Blood and organ samples were collected under a fasting condition. The body weight and blood glucose levels were measured. Hepatic enzymes were determined using a commercial kit, protein levels were estimated by Bradford's method, and plasma insulin was assayed by an ELISA kit. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated by the TBA-Wills method and Ellman's method, respectively. RESULTS: Ethanolic extract of Murraya koenigii showed a significant reduction in blood glucose level at both doses, 200 and 400 mg/kg b.w. In addition, Murraya koenigii exhibited a profound antioxidant effect with decreased MDA level and increased GSH level, particularly at the 200 mg/kg b.w. and significantly decreased the HOMA-IR index. CONCLUSIONS: The present study reveals that Murraya koenigii possesses antidiabetic activity and antioxidant effects on STZ-NA induced diabetes mellitus.