Effect of 4-Phenylbutyric Acid and Tauroursodeoxycholic Acid on Magnesium and Calcium Metabolism in Streptozocin-Induced Type 1 Diabetic Mice

Recent evidence has identified a role of micronutrients, such as magnesium (Mg(2+)) and calcium (Ca(2+)), in glycemic control. 4-Phenylbutyric acid (PBA) and tauroursodeoxycholic acid (TUDCA) are molecular chaperones that can improve protein folding and alleviate endoplasmic reticulum (ER) stress. Increasingly, research is focusing on the association between molecular chaperones and micronutrients. This study established and characterized a mouse model of type 1 diabetes (T1D) and investigated the effect of PBA and TUDCA on Mg(2+) and Ca(2+) metabolism in these mice. T1D was established in Friend virus B-type mice using multiple low doses of streptozotocin. Mice were administered chaperones. Mg(2+)and Ca(2+) levels in tissues and serum were detected using acid digestion and ICP-MS. At 2 weeks and 2 months after chaperone administration was initiated, Mg(2+) levels in the heart, liver, kidney, and serum and Ca(2+) levels in spleen and serum of T1D mice were significantly decreased compared with controls; Ca(2+) levels in the kidney and muscle of T1D mice were significantly increased; Mg(2+) and Ca(2+) levels in the heart, liver, kidney, muscle, spleen, and serum were positively correlated in control and T1D mice; and PBA restored renal Mg(2+) levels to normal values and TUDCA restored hepatic, renal, and serum Mg(2+) levels and renal and serum Ca(2+) levels to normal values in T1D mice. PBA restored muscular Ca(2+) levels to normal values in T1D mice at 2 months after chaperone or vehicle administration was initiated. Further research is required to investigate the underlying mechanisms by which chaperones regulate micronutrients in diabetes.