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Diabetes 54:1385-1391, 2005
© 2005 by the American Diabetes Association, Inc.

Uncoupling Protein 1 Is Necessary for Norepinephrine-Induced Glucose Utilization in Brown Adipose Tissue

Ken-ichi Inokuma1, Yuko Ogura-Okamatsu1, Chitoku Toda1, Kazuhiro Kimura1, Hitoshi Yamashita2, and Masayuki Saito1

1 Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan
2 Department of Molecular Genetics, National Institute for Longevity Sciences, Obu, Japan

Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the ß-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial uncoupling protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.

Address correspondence and reprint requests to Masayuki Saito, PhD, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. E-mail: saito{at}vetmed.hokudai.ac.jp

Abbreviations: 2-DG, 2-deoxyglucose; AMP kinase, AMP-activated protein kinase; BAT, brown adipose tissue; FFA, free fatty acid; NE, norepinephrine; UCP, uncoupling protein; WAT, white adipose tissue


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