Effect of Tauroursodeoxycholic Acid and 4-Phenylbutyric Acid on Metabolism of Copper and Zinc in Type 1 Diabetic Mice Model

Alternations of copper (Cu) and zinc (Zn) status in diabetes have received a great attention. Tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyric acid (PBA) could alleviate the increased endoplasmic reticulum (ER) stress and prevent insulin resistance. This study aimed to investigate the effect of TUDCA and PBA on metabolism of Cu and Zn in diabetic mice model. Diabetes was induced by streptozotocin in FVB mice treated with and without TUDCA and PBA. Determination of Cu and Zn in tissues and serum by acid digestion was followed by ICP-MS. The renal and serum Cu levels were significantly higher, while the hepatic Cu and Zn levels were significantly decreased in the diabetic mice at 2 weeks and 2 months after diabetes onset. The increase of cardiac Cu together with the decrease of muscular Zn was found in the diabetic mice only at 2 months. Cu levels were positively correlated with Zn in the heart, liver, kidney, muscle, spleen, and serum of diabetic and control mice at both 2 weeks and 2 months. Both PBA and TUDCA reduced serum Zn, and PBA reduced hepatic Cu to normal levels in the diabetic mice at two time points, while PBA normalized serum Cu in the diabetic mice only at 2 months. PBA increased hepatic Zn to normal levels in the diabetic mice at 2 weeks, while it partially increased hepatic Zn in the same group at 2 months. Therefore, maintaining homeostasis of Cu and Zn by TUDCA and PBA in diabetes needs to be received with special attention.