HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/E643    most recent 00456.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (15) Citing Articles via Google Scholar Google Scholar Articles by Yamaguchi, S. Articles by Ishida, H. Search for Related Content PubMed PubMed Citation Articles by Yamaguchi, S. Articles by Ishida, H.

Activators of AMP-activated protein kinase enhance GLUT4 translocation and its glucose transport activity in 3T3-L1 adipocytes

¹Third Department of Internal Medicine and ²Department of Biochemistry, Kyorin University, Mitaka, Tokyo, Japan

Submitted 27 October 2004 ; accepted in final form 5 May 2005

To determine whether the increase in glucose uptake following AMP-activated protein kinase (AMPK) activation in adipocytes is mediated by accelerated GLUT4 translocation into plasma membrane, we constructed a chimera between GLUT4 and enhanced green fluorescent protein (GLUT4-eGFP) and transferred its cDNA into the nucleus of 3T3-L1 adipocytes. Then, the dynamics of GLUT4-eGFP translocation were visualized in living cells by means of laser scanning confocal microscopy. It was revealed that the stimulation with 5-aminoimidazole-4-carboxamide-1--D-ribofuranoside (AICAR) and 2,4-dinitrophenol (DNP), known activators of AMPK, promptly accelerates its translocation within 4 min, as was found in the case of insulin stimulation. The insulin-induced GLUT4 translocation was markedly inhibited after addition of wortmannin (P < 0.01). However, the GLUT4 translocation through AMPK activators AICAR and DNP was not affected by wortmannin. Insulin- and AMPK-activated translocation of GLUT4 was not inhibited by SB-203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK). Glucose uptake was significantly increased after addition of AMPK activators AICAR and DNP (P < 0.05). AMPK- and insulin-stimulated glucose uptake were similarly suppressed by wortmannin (P < 0.05–0.01). In addition, SB-203580 also significantly prevented the enhancement of glucose uptake induced by AMPK and insulin (P < 0.05). These results suggest that AMPK-activated GLUT4 translocation in 3T3-L1 adipocytes is mediated through the insulin-signaling pathway distal to the site of activated phosphatidylinositol 3-kinase or through a signaling system distinct from that activated by insulin. On the other hand, the increase of glucose uptake dependent on AMPK activators AICAR and DNP would be additionally due to enhancement of the intrinsic activity in translocated GLUT4 protein, possibly through a p38 MAPK-dependent mechanism.

glucose transporter 4; mitogen-activated protein kinase; phosphatidylinositol 3-kinase; enhanced green fluorescent protein

This article has been cited by other articles:

				L. Feng, L. Gao, Q. Guan, X. Hou, Q. Wan, X. Wang, and J. Zhao Long-term moderate ethanol consumption restores insulin sensitivity in high-fat-fed rats by increasing SLC2A4 (GLUT4) in the adipose tissue by AMP-activated protein kinase activation J. Endocrinol., October 1, 2008; 199(1): 95 - 104. [Abstract] [Full Text] [PDF]

				R.-Y. Su, K.-H. Chi, D.-Y. Huang, M.-H. Tai, and W.-W. Lin 15-deoxy-{Delta}12,14-prostaglandin J2 up-regulates death receptor 5 gene expression in HCT116 cells: involvement of reactive oxygen species and C/EBP homologous transcription factor gene transcription Mol. Cancer Ther., October 1, 2008; 7(10): 3429 - 3440. [Abstract] [Full Text] [PDF]

				V. Kaddai, T. Gonzalez, M. Bolla, Y. Le Marchand-Brustel, and M. Cormont The nitric oxide-donating derivative of acetylsalicylic acid, NCX 4016, stimulates glucose transport and glucose transporters translocation in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E162 - E169. [Abstract] [Full Text] [PDF]

				K. Takahashi, S. Yamaguchi, T. Shimoyama, H. Seki, K. Miyokawa, H. Katsuta, T. Tanaka, K. Yoshimoto, H. Ohno, S. Nagamatsu, et al. JNK- and I{kappa}B-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E898 - E909. [Abstract] [Full Text] [PDF]

				D. Williams, S. W. Hicks, C. E. Machamer, and J. E. Pessin Golgin-160 Is Required for the Golgi Membrane Sorting of the Insulin-responsive Glucose Transporter GLUT4 in Adipocytes Mol. Biol. Cell, December 1, 2006; 17(12): 5346 - 5355. [Abstract] [Full Text] [PDF]