Regulation of Insulin Sensitivity by Phosphorus

Dietary phosphorus excess as a result of the ever growing consumption of highly processed foods has been associated with developments of ageing related diseases such as diabetes and obesity in the general human population. Insulin resistance is the main feature of aged human population especially in patients with type 2 diabetes and some people with obesity. Thus, the study of a low phosphorus diet on glucose homeostasis such as insulin resistance and glucose tolerance is of great interest. Here, we investigated glucose homeostasis in male and female 129Sv mice fed with low phosphorus diet (0.2% of Pi) vs. control diet (0.4% of Pi). Interestingly, the fasting basal glucose level dropped significantly in male mice after being fed with low Pi diet for 4 weeks. In addition, low Pi diet significantly enhanced insulin sensitivity in both male and female mice. Furthermore, low Pi diet lowered serum Pi levels in mice of both genders without interrupting the growing pattern of body weights during the 10-week feeding period. Examination of proteins with Western Blot revealed that low Pi diet significantly enhanced insulin receptor β (IRβ) levels in skeletal muscles. In vitro experiments indicated that low Pi enhanced and high Pi inhibited insulin signals such as tyrosine phosphorylation of IRβ (Tyr1150/1151) and serine phosphorylation of Akt (Ser473) in primary culture of human skeletal muscle cells (HSkMCs). In addition, low Pi increased and high Pi decreased insulin-induced glucose uptake in HSkMCs. Therefore, these data indicate that low Pi diet regulates glucose homeostasis, partly via enhancing insulin sensitivity through upregulating insulin signals and insulin-induced glucose uptake in skeletal muscles.