Vitamin D3 improves glucose metabolism and attenuates inflammation in prediabetic human and mice

Abstract

Prediabetes is a crucial stage for prevention and treatment of diabetes, and vitamin D (VD) has been found to be linked to the development of prediabetes and diabetes. Thus, we aimed to identify the effect of VD supplementation on glucose metabolism in prediabetic participants and mice. A 1:1 paired design of randomized, placebo-controlled trial with 1600 IU/day VD3 or placebo was administered to individuals with prediabetes, two-way repeated-measures ANCOVA was used to analyze glycolipid and inflammatory factors. A high-fat diet induced prediabetic KKay mice were utilized to evaluate the effects of VD3 with 16 weeks supplementation. Generalized estimation equation, one way ANOVA were used to analyze continuous monitoring indexes and terminal indexes, respectively. Exercise capacity, skeletal muscle pathological features and relevant proteins were examined. The clinical results showed that VD3 could improve insulin secretion and decrease inflammation. Results of KKay mice exhibited that VD3 not only ameliorate glycolipid metabolism and inflammatory indicators, but also regulated pathological changes of skeletal muscle and exercise capacity. Mechanistically, our results demonstrated that VD3 could inhibit the TLR4/NFκB and activate PI3K/AKT signaling pathway. Collectively, the study indicated that VD3 exerts its beneficial effects by inhibiting TLR4/NFκB to decrease inflammatory response, and activating PI3K/AKT signaling pathway to regulate glucose homeostasis.