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

Front Endocrinol (Lausanne). 2023 May 31:14:1089298. doi: 10.3389/fendo.2023.1089298. eCollection 2023.

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.

Keywords: 25-hydroxyergocalciferol; diabetes mellitus; high-fat diet; inflammation; insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Cholecalciferol / pharmacology
  • Diabetes Mellitus, Type 2* / metabolism
  • Dietary Supplements / analysis
  • 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

Substances

  • NF-kappa B
  • PPAR gamma
  • Blood Glucose
  • Vitamin D
  • Vitamins
  • Cholecalciferol

Grants and funding

This study was funded by Grants from the Ministry of Education and Culture, Republic of Indonesia No. NKB-804/UN2.RST/HKP.05.00/2022.