The Effects of Uncoupling Protein 3 Overexpression on Glucose Metabolism in OLETF Rats in Vivo and Cultured Skeletal Muscle Cells in Vitro.

Han,  Jeong Hee; Park,  Hye Seon; Koh,  Jung Min; Kim,  Ha Young; Kang,  Ho Kyung; Lee,  In Kyu; Park,  Joong Yeol; Hong,  Sung Kwan; Lee,  Jae Dam; Lee,  Ki Up

Original Article

Korean Diabetes Journal 2001;25(6):460-468.
Published online December 1, 2001.

The Effects of Uncoupling Protein 3 Overexpression on Glucose Metabolism in OLETF Rats in Vivo and Cultured Skeletal Muscle Cells in Vitro.

Jeong Hee Han, Hye Seon Park, Jung Min Koh, Ha Young Kim, Ho Kyung Kang, In Kyu Lee, Joong Yeol Park, Sung Kwan Hong, Jae Dam Lee, Ki Up Lee

¹Department of Internal Medicine, College of Medicine, University of Ulsan, Korea.
²Asan Institute for Life Sciences and Technology, Korea.
³Department of Internal Medicine, Keimyung University, Korea.
⁴Department of Biochemistry, College of Medicine, University of Ulsan, Korea.

Abstract

BACKGROUND
UCP3 is a mitochondrial membrane protein expressed selectively in the skeletal muscle and brown adipose tissue. Since the skeletal muscle is the main organ determining insulin sensitivity in the body, it was hypothesized that UCP3 overexpression in skeletal muscle cells would improve glucose metabolism. METHODS: An adenovirus-UCP3 was produced by a recombinant DNA method. OLETF rats were divided into 2 groups. Four rats were injected with the adenovirus- UCP3 (UCP3 group) and others were injected with the adenovirus (control group) in the skeletal muscle. The UCP3 group was provided with the same quantity of food as that consumed by the control group on the previous day. Insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp method. In a separate experiment, glucose transport and glycogen synthesis we evaluated in C2C12 cells transfected with ether an adenovirus or the adenovirus-UCP3. RESULTS: The insulin sensitivity improved significantly and the body weight decreased in the UCP3 group. The glucose transport and glycogen synthesis were higher in the UCP3-C2C12 skeletal muscle cells at the basal state. After insulin treatment, glucose transport and glycogen synthesis were also higher in the UCP3-C2C12 cells but the increments were reduced after treatment with wortmannin, a PI3K inhibitor. CONCLUSION: Insulin sensitivity was higher in the UCP3-overexpressed OLETF rats in the in vivo study. UCP3 transfection also increased glucose transport and glycogen synthesis in the cultured skeletal muscle cells by a PI3K dependent mechanism.

Key Words: UCP3, Glucose transport, Glycogen synthesis, PI3K