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

Abstract

BackgroundPrediabetes 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.MethodThe 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.ResultsVitamin 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.ConclusionVitamin 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.

Gastrodin ameliorates neuroinflammation in Alzheimer’s disease mice by inhibiting NF-κB signaling activation via PPARγ stimulation

“…In terms of antiinflammation, PPARγ is expressed in both monocytes macrophages, which, after activation, inhibits monocytes or macrophages from producing inflammatory mediators IL-1β, IL-6, TNF-α, as well as inducible nitric oxide synthase [16]. PPARγ inhibits the proinflammatory gene expressions at the transcriptional level by antagonizing the activities of transcription factors like NF-κB, AP-1 and STAT1 [17], and its agonists can effectively inhibit the inflammatory molecule production mediated by microglia and astrocytes in the central nervous system [18,19]. GAS, as a small-molecule liposoluble monomer compound extracted from Rhizoma Gastrodiae with good druggability, has recently been approved as a therapeutic drug.…”

Environmental Temperature, Other Climatic Variables, and Cardiometabolic Profile in Acute Myocardial Infarction

“…Accordingly, in a subgroup of AMI patients (n = 123), in which vitamin D tests were available, levels of 25(OH)D were lower in T2D compared with non-T2D patients (mean:14 ± 8 vs. 22 ± 11 mg/dL, p ≤ 0.001), and the percentage of patients with 25(OH)D marked severe (< 10 mg/dL) was more than tripled in T2D compared with non-T2D patients (48% vs. 13%, p < 0.001). Moreover, other data suggested that the odds of having insulin resistance was significantly greater for subjects in the lowest quartile of 25(OH)D compared to the other quartiles combined, likely by modulation of several key pathways affecting glucose metabolism (e.g., increasing proinflammatory cytokines and oxidative stress affecting insulin signaling and epigenetic regulation of gene expression, as well as RAAS) [28][29][30][31]. It has been also suggested that low vitamin D is associated with atherogenic blood lipid profiles, whereas its supplementation is able to lower the levels of total cholesterol, triglycerides, and LDL cholesterol, as well as to increase HDL cholesterol [32].…”

Vitamin D attenuates diabetic myocardial injury via the Erbb4/ferroptosis axis

“…The effects of vitamin D on prediabetes present a contentious landscape in existing studies. Some studies suggest that VD supplementation during prediabetic stage with notably low VD levels improves insulin sensitivity, diminishes the risk of diabetes development, and improves insulin resistance in prediabetic rodents, while others have shown that treatment of VD 3 for 24 consecutive months does not improve OGTT-derived indices of β-cell function in prediabetic patients [18–20] . Correspondingly, KKAy mice represent a spontaneously diabetic model characterized by hyperglycemia, impaired glucose tolerance, insulin resistance, and obesity induced by a high-fat diet.…”