To investigate the impact of vitamin D deficiency on insulin resistance and abnormal glucose homeostasis in obesity.Methods and results:
Sixty male C57BL/6 mice (3 months old) were fed a control diet (C—10% energy as fat) or a high-fat diet (HF—50% energy as fat), with or without vitamin D, for 8 weeks. There was no difference in body mass between the HF and HF/VitD- groups. Vitamin D deficiency (VitD) in the diet-induced obese mice increased hyperinsulinemia (p = 0.04), hyperleptinemia (p = 0.0002), insulin resistance (HOMA-IR, p = 0.04), and islet changes, including alpha and beta cell disarray. In the insulin signaling pathway, insulin receptor substrate 2 expression was upregulated in the C/VitD- group (p = 0.001) and downregulated in the HF/VitD- group (p = 0.009). Interestingly, forkhead box protein O1 expression was higher in the HF/VitD- group than in the HF group (p = 0.03), and pancreatic and duodenal homeobox 1 expression was lower in the HF/VitD-group than in the HF group (p = 0.025), indicating that the HF diet and vitamin D deficiency influenced the downregulation of the expression of these proteins (two-way ANOVA, p < 0.0001).Conclusion:
Vitamin D deficiency exacerbated the adverse structural and physiological remodeling of pancreatic islets due to obesity, contributing to abnormal glucose homeostasis.