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Acute reversal of lipid-induced muscle insulin resistance is associated with rapid alteration in PKC-theta localization


Muscle insulin resistance in the chronic high-fat-fed rat is associated with increased membrane translocation and activation of the novel, lipid-responsive, protein kinase C (nPKC) isozymes PKC-theta and -epsilon. Surprisingly, fat-induced insulin resistance can be readily reversed by one high-glucose low-fat meal, but the underlying mechanism is unclear. Here, we have used this model to determine whether changes in the translocation of PKC-theta and -epsilon are associated with the acute reversal of insulin resistance. We measured cytosol and particulate PKC-alpha and nPKC-theta and -epsilon in muscle in control chow-fed Wistar rats (C) and 3-wk high-fat-fed rats with (HF-G) or without (HF-F) a single high-glucose meal. PKC-theta and -epsilon were translocated to the membrane in muscle of insulin-resistant HF-F rats. However, only membrane PKC-theta was reduced to the level of chow-fed controls when insulin resistance was reversed in HF-G rats [% PKC-theta at membrane, 23.0 +/- 4.4% (C); 39.7 +/- 3.4% (HF-F, P < 0.01 vs. C); 22.5 +/- 2.7% (HF-G, P < 0.01 vs. HF-F), by ANOVA]. We conclude that, although muscle localization of both PKC-epsilon and PKC-theta are influenced by chronic dietary lipid oversupply, PKC-epsilon and PKC-theta localization are differentially influenced by acute withdrawal of dietary lipid. These results provide further support for an association between PKC-theta muscle cellular localization and lipid-induced muscle insulin resistance and stress the labile nature of high-fat diet-induced insulin resistance in the rat.

Type Journal
ISBN 0193-1849 (Print)
Authors Bell, K. S.;Schmitz-Peiffer, C.;Lim-Fraser, M.;Biden, T. J.;Cooney, G. J.;Kraegen, E. W. :
Garvan Authors Prof Gregory Cooney , Prof Ted Kraegen
Published Date 2000-01-01 00:00:00
Published Volume 279
Published Issue 5
Published Pages E1196-201
Status Published In-print