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

Qi Zhou,Jiancheng Xu,Baorong Chi,Di Wang

doi:10.1007/s12011-015-0474-5

Qi Zhou, Jiancheng Xu + Show 2 more

Open Access

https://doi.org/10.1007/s12011-015-0474-5

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Abstract

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.

Highlights

Diabetes mellitus (DM) has become one of the most severe endocrine metabolic disorders in the world
Maintaining homeostasis of Cu and Zn by Tauroursodeoxycholic acid (TUDCA) and phenylbutyric acid (PBA) in diabetes needs to be received with special attention
The mice were randomly divided into six groups (n = 14 in each group), namely, nondiabetic control mice (CON), diabetic mice (DM), diabetic mice treated with PBA (PBA + DM) or TUDCA (TUDCA + DM), and nondiabetic control mice treated with PBA (PBA) or TUDCA (TUDCA)

Summary

Introduction

Diabetes mellitus (DM) has become one of the most severe endocrine metabolic disorders in the world. Diabetes damages multiple organs to induce serious complications such as diabetic retinopathy, neuropathy, and nephropathy that can result in the disability and mortality for diabetic patients [1]. Excessive caloric intake and high-energy diet quality are major driving forces behind escalating diabetes and the appearance of epidemics worldwide [2]. As an essential component of the daily diet intake, trace elements are important for the occurrence and progression of diabetes. Alternations in trace element status and increased oxidative stress in diabetes may contribute to insulin resistance and the development of diabetes and diabetic complications [3, 4]. Progression of diabetes may lead to perturbation in trace element metabolism and homeostasis [5]

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