AJP - Endocrinology and Metabolism, Vol 272, Issue 2 E326-E331, Copyright © 1997 by American Physiological Society

ARTICLES

Roles of PI 3-kinase and Ras on insulin-stimulated glucose transport in 3T3-L1 adipocytes

H. Katagiri, T. Asano, K. Inukai, T. Ogihara, H. Ishihara, Y. Shibasaki, T. Murata, J. Terasaki, M. Kikuchi, Y. Yazaki and Y. Oka
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Japan.

The dominant negative p85alpha regulatory subunit (delta p85alpha) of phosphatidylinositol (PI) 3-kinase or dominant negative Ras (N17Ras) was overexpressed in 3T3-L1 adipocytes using an adenovirus-mediated gene transduction system. Functional expression of delta p85alpha and N17Ras was confirmed by marked inhibition of insulin-stimulated PI 3-kinase activity and mitogen-activated protein kinase activity, respectively. N17Ras expression did not affect glucose transport activity, whereas delta p85alpha expression inhibited insulin-stimulated glucose transport with impairment of GLUT-4 translocation, although inhibition of glucose transport activity was less remarkable than that of PI 3-kinase activity in delta p85alpha-expressing cells. Thus the Ras signaling pathway does not play a major part in either translocation or intrinsic activity of glucose transporters, but PI 3-kinase activation, via phosphotyrosyl proteins and heterodimeric PI 3-kinase, plays a pivotal role in insulin-stimulated glucose transport. However, a discrepancy was observed between PI 3-kinase activity and glucose transport activity, suggesting a possibility that a different pathway(s) is involved in insulin-stimulated intrinsic activity of glucose transporters.

This article has been cited by other articles:

				A. W. Harmon, D. S. Paul, and Y. M. Patel MEK inhibitors impair insulin-stimulated glucose uptake in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E758 - E766. [Abstract] [Full Text] [PDF]

				M. Tsuru, H. Katagiri, T. Asano, T. Yamada, S. Ohno, T. Ogihara, and Y. Oka Role of PKC isoforms in glucose transport in 3T3-L1 adipocytes: insignificance of atypical PKC Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E338 - E345. [Abstract] [Full Text] [PDF]

				T. Yamada, H. Katagiri, T. Asano, M. Tsuru, K. Inukai, H. Ono, T. Kodama, M. Kikuchi, and Y. Oka Role of PDK1 in insulin-signaling pathway for glucose metabolism in 3T3-L1 adipocytes Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1385 - E1394. [Abstract] [Full Text] [PDF]

				R. Aikawa, M. Nawano, Y. Gu, H. Katagiri, T. Asano, W. Zhu, R. Nagai, and I. Komuro Insulin Prevents Cardiomyocytes From Oxidative Stress-Induced Apoptosis Through Activation of PI3 Kinase/Akt Circulation, December 5, 2000; 102(23): 2873 - 2879. [Abstract] [Full Text] [PDF]

				S. A. Moodie, J. Alleman-Sposeto, and T. A. Gustafson Identification of the APS Protein as a Novel Insulin Receptor Substrate J. Biol. Chem., April 16, 1999; 274(16): 11186 - 11193. [Abstract] [Full Text] [PDF]

				G. Sweeney, R. Somwar, T. Ramlal, A. Volchuk, A. Ueyama, and A. Klip An Inhibitor of p38 Mitogen-activated Protein Kinase Prevents Insulin-stimulated Glucose Transport but Not Glucose Transporter Translocation in 3T3-L1 Adipocytes and L6 Myotubes J. Biol. Chem., April 9, 1999; 274(15): 10071 - 10078. [Abstract] [Full Text] [PDF]

				A. P. Feranchak, R. M. Roman, E. M. Schwiebert, and J. G. Fitz Phosphatidylinositol 3-Kinase Contributes to Cell Volume Regulation through Effects on ATP Release J. Biol. Chem., June 12, 1998; 273(24): 14906 - 14911. [Abstract] [Full Text] [PDF]

				T. Ogihara, B.-C. Shin, M. Anai, H. Katagiri, K. Inukai, M. Funaki, Y. Fukushima, H. Ishihara, K. Takata, M. Kikuchi, et al. Insulin Receptor Substrate (IRS)-2 Is Dephosphorylated More Rapidly than IRS-1 via Its Association with Phosphatidylinositol 3-Kinase in Skeletal Muscle Cells J. Biol. Chem., May 9, 1997; 272(19): 12868 - 12873. [Abstract] [Full Text] [PDF]