Vitamin D-Cellular Ca2+ link to obesity and diabetes

Abstract

The vitamin D hormone 1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃)-induced cellular Ca²⁺ signals regulate apoptosis in adipocytes and insulin secretion from pancreatic β-cells, and low vitamin D status is considered a risk factor for obesity and type 2 diabetes. The anti-obesity effects of 1,25(OH)₂D₃ in mature adipocytes are determined by its activity to generate, via multiple Ca²⁺ signaling pathways, a sustained increase in intracellular Ca²⁺ followed by activation of the Ca²⁺-dependent initiators and effectors of apoptosis. In pancreatic β-cells, 1,25(OH)₂D₃ induces synchronous Ca²⁺ oscillations, which pattern pulsatile insulin secretion from these cells. An increased intake of vitamin D₃ in a high fat diet-induced obesity mouse model is associated with a decreased weight of white adipose tissue due to induction of apoptosis and the improved blood markers related to adiposity, diabetes, and vitamin D status (plasma concentrations of glucose, insulin, adiponectin, 25-hydroxyvitamin D, and 1,25(OH)₂D₃). High vitamin D₃ intake is also effective in increasing the mineral content of growing bone in obese mice via regulatory effects mediated by 1,25(OH)₂D₃-parathyroid hormone axis. The 1,25(OH)₂D₃-dependent cellular Ca²⁺ signaling can be important for maintaining the normal levels of apoptosis in adipose tissue and insulin secretion from pancreatic β-cells. An increased intake of vitamin D may contribute to the prevention of obesity, type 2 diabetes, and bone disorders associated with these diseases.

Keywords: 1,25-Dihydroxyvitamin D(3); Apoptosis; Intracellular Ca(2+); Obesity; Type 2 diabetes; Vitamin D status.