Department of Medical Pharmacy, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.
Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Front Endocrinol (Lausanne). 2023 May 31;14:1089298. doi: 10.3389/fendo.2023.1089298. eCollection 2023.
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.
糖尿病前期是一种中间高血糖状态，可能会发展为 2 型糖尿病。维生素 D 缺乏与胰岛素抵抗和糖尿病密切相关。本研究旨在探讨 D 补充剂的作用及其对糖尿病前期大鼠胰岛素抵抗的可能作用机制。
本研究共纳入 24 只雄性 Wistar 大鼠，随机分为健康对照组和 18 只糖尿病前期大鼠。糖尿病前期大鼠采用高脂肪高葡萄糖饮食（HFD-G）联合小剂量链脲佐菌素诱导。糖尿病前期大鼠再随机分为 3 组，每组 12 周治疗：一组不治疗，一组给予 100 IU/kg BW 的维生素 D3，一组给予 1000 IU/kg BW 的维生素 D3。整个 12 周治疗期间持续给予高脂肪高葡萄糖饮食。在补充期结束时，测量葡萄糖控制参数、炎症标志物以及 IRS1、PPARγ、NF-κB 和 IRS1 的表达。
维生素 D3 呈剂量依赖性改善葡萄糖控制参数，表现为空腹血糖（FBG）、口服葡萄糖耐量试验（OGTT）、糖化白蛋白、胰岛素水平和胰岛素抵抗标志物（HOMA-IR）降低。组织学分析显示，维生素 D 补充可减少胰岛 Langerhans 变性。维生素 D 还增强了 IL-6/IL-10 的比值，降低 IRS1 丝氨酸 307 磷酸化，增加 PPARγ 表达，降低 NF-κB p65 丝氨酸 536 磷酸化。
维生素 D 补充可降低糖尿病前期大鼠的胰岛素抵抗。这种降低可能是由于维生素 D 对 IRS、PPARγ 和 NF-κB 表达的影响。
