Vitamin D is glucoprotective in aging males but not females.

Vitamin D supplementation is linked to many beneficial health outcomes in the geriatric population, such as decreased mortality, epigenetic aging, and fracture risk. Conversely, type 2 diabetes is strongly linked to vitamin D deficiency in older adults. However, there is a discrepancy between clinical trials in adults on the efficacy of vitamin D treatment in prediabetes and diabetes. In addition, human data indicates there may be sexual dimorphism in the effect of vitamin D deficiency on dysglycemia that is more pronounced in men. These incongruities may be due to our limited understanding of the underlying mechanisms of vitamin D in glucose homeostasis among its vast target tissues across the body. Here we describe the physiological effects of vitamin D supplementation in an aged, non-obese mouse model on glucose homeostasis and associated tissue-specific gene regulation. Specifically, we found that 1) increased dietary vitamin D intake can improve glucose regulation in lean, aged male mice, and 2) these male mice also had decreased Glut4 and Insr expression in a diet low in vitamin D in various tissues indicating that dietary vitamin D may be a sex-specific key mediator in regulating glucose tolerance and protecting against insulin resistance.