Vitamin D supplementation alleviates insulin resistance in prediabetic rats by modifying IRS-1 and PPARγ/NF-κB expressions

• Published in: Frontiers in endocrinology (Lausanne) Vol. 14; p. 1089298
• Main Authors: Krisnamurti, Desak Gede Budi, Louisa, Melva, Poerwaningsih, Erni H, Tarigan, Tri Juli Edi, Soetikno, Vivian, Wibowo, Heri, Nugroho, Christian Marco Hadi
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 31.05.2023
• Subjects: 25-hydroxyergocalciferol; Animals; Blood Glucose - analysis; Cholecalciferol - pharmacology; diabetes mellitus; Diabetes Mellitus, Type 2 - metabolism; Dietary Supplements - analysis; Endocrinology; high-fat diet; inflammation; Insulin Resistance; Male; NF-kappa B; PPAR gamma; Prediabetic State - drug therapy; Prediabetic State - metabolism; Rats; Rats, Wistar; Vitamin D; Vitamins - pharmacology; Vitamins - therapeutic use; 25-hydroxyergocalciferol; diabetes mellitus; inflammation; insulin resistance; high-fat diet
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2023.1089298

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. 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. 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. 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.