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

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Google Scholar Google Scholar Articles by Standaert, M. L. Articles by Pollet, R. J. Search for Related Content PubMed PubMed Citation Articles by Standaert, M. L. Articles by Pollet, R. J. Social Bookmarking                      What's this?

J. Biol. Chem., Vol. 263, Issue 18, 8696-8705, 06, 1988

Insulin-induced glycerolipid mediators and the stimulation of glucose transport in BC3H-1 myocytes

ML Standaert, RV Farese, DR Cooper and RJ Pollet
Department of Medicine, University of South Florida, Tampa 33612.

We have previously demonstrated that insulin stimulates glycerolipid synthesis and phospholipid hydrolysis in BC3H-1 myocytes, resulting in the generation of membrane diacylglycerol, a known cellular mediator. This led us to the original proposal that diacylglycerol may contribute to the mediation of insulin action, especially stimulation of glucose transport. The fact that agents such as phenylephrine and phorbol esters, which increase or act as membrane diacylglycerols, are fully active in stimulating glucose transport in this tissue lent further support to this proposal. In this paper, we demonstrate that the diacylglycerol analogues PMA (4 beta-phorbol 12-myristate 13-acetate) and mezerein (both possessing 12 beta- and 13 alpha-O-linked substituents as well as a 4 beta-hydroxyl group) each increase the Vmax of the glucose transporter as does insulin. Diacylglycerol generated by the addition of phospholipase C also stimulates glucose uptake to a maximum which is equal and nonadditive to that of insulin, while addition of the narrowly active phosphatidylinositol-specific phospholipase C which generates the putative phosphoinositol-glycan mediator of Saltiel et al. (Saltiel, A., Fox, J., She Lin, P., and Cutrecasas, P. (1986) Science 233, 967-972) stimulates pyruvate dehydrogenase in these cells without any effect on glucose uptake. Pretreatment of the myocytes with PMA resulted in desensitization of subsequent glucose uptake to stimulation by phenylephrine, but had no effect on stimulation of glucose uptake by phospholipase C or by insulin, indicating that PMA pretreatment primarily desensitizes agonist-induced polyphosphoinositide hydrolysis which, as we have previously shown, is not involved in the insulin-induced generation of diacylglycerol. This was confirmed by the absence of intracellular Ca2+ mobilization during insulin administration, as measured by the sensitive fluorescent probe fura-2 in attached monolayer BC3H-1 myocytes. Furthermore, we have shown that insulin-generated diacylglycerol satisfies several criteria for a mediator of insulin action, including the demonstration that insulin-stimulated endogenous diacylglycerol generation is antecedent to glucose transport and has an identical insulin dose-response curve and moreover that the magnitude and time course of subsequent stimulation of glucose transport is reproduced by the addition of the simple exogenous diacylglyerol, dioctanoylglycerol, in the complete absence of the hormone. These results establish a central role for insulin-induced glycerolipid metabolism in mediating insulin-stimulated glucose transport in BC3H-1 myocytes.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. C. Wright, P. C. Geiger, M. J. Rheinheimer, D. H. Han, and J. O. Holloszy Phorbol esters affect skeletal muscle glucose transport in a fiber type-specific manner Am J Physiol Endocrinol Metab, August 1, 2004; 287(2): E305 - E309. [Abstract] [Full Text] [PDF]

				R. V. Farese Insulin-Sensitive Phospholipid Signaling Systems and Glucose Transport. Update II Experimental Biology and Medicine, April 1, 2001; 226(4): 283 - 295. [Abstract] [Full Text]

				G. Bandyopadhyay, M. L. Standaert, L. Galloway, J. Moscat, and R. V. Farese Evidence for Involvement of Protein Kinase C (PKC)-{zeta} and Noninvolvement of Diacylglycerol-Sensitive PKCs in Insulin-Stimulated Glucose Transport in L6 Myotubes Endocrinology, November 1, 1997; 138(11): 4721 - 4731. [Abstract] [Full Text] [PDF]

				C. E. Chalfant, H. Mischak, J. E. Watson, B. C. Winkler, J. Goodnight, R. V. Farese, and D. R. Cooper Regulation of Alternative Splicing of Protein Kinase C[IMAGE] by Insulin J. Biol. Chem., June 2, 1995; 270(22): 13326 - 13332. [Abstract] [Full Text] [PDF]