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Am J Physiol Endocrinol Metab 282: E1239-E1244, 2002. First published February 19, 2002; doi:10.1152/ajpendo.00455.2001
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Vol. 282, Issue 6, E1239-E1244, June 2002

Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes

Hideyuki Sakoda1, Takehide Ogihara2, Motonobu Anai1, Midori Fujishiro2, Hiraku Ono1, Yukiko Onishi1, Hideki Katagiri3, Miho Abe2, Yasushi Fukushima2, Nobuhiro Shojima2, Kouichi Inukai4, Masatoshi Kikuchi1, Yoshitomo Oka3, and Tomoichiro Asano2

1 Institute for Adult Disease, Asahi Life Foundation, Tokyo 116; 2 Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113; 3 Department of Internal Medicine, University of Tohoku, Sendai 980-8575; and 4 Fourth Department of Internal Medicine, Saitama Medical School, Moroyama, Saitama, Japan

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) reportedly activates AMP-activated protein kinase (AMPK) and stimulates glucose uptake by skeletal muscle cells. In this study, we investigated the role of AMPK in AICAR-induced glucose uptake by 3T3-L1 adipocytes and rat soleus muscle cells by overexpressing wild-type and dominant negative forms of the AMPKalpha 2 subunit by use of adenovirus-mediated gene transfer. Overexpression of the dominant negative mutant had no effect on AICAR-induced glucose transport in adipocytes, although AMPK activation was almost completely abolished. This suggests that AICAR-induced glucose uptake by 3T3-L1 adipocytes is independent of AMPK activation. By contrast, overexpression of the dominant negative AMPKalpha 2 mutant in muscle markedly suppressed both AICAR-induced glucose uptake and AMPK activation, although insulin-induced uptake was unaffected. Overexpression of the wild-type AMPKalpha 2 subunit significantly increased AMPK activity in muscle but did not enhance glucose uptake. Thus, although AMPK activation may not, by itself, be sufficient to increase glucose transport, it appears essential for AICAR-induced glucose uptake in muscle.

AMP-activated protein kinase; 5-aminoimidazole-4-carboxamide ribonucleoside; exercise


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