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.
Bell
K S
KS
Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia.
Schmitz-Peiffer
C
C
Lim-Fraser
M
M
Biden
T J
TJ
Cooney
G J
GJ
Kraegen
E W
EW
D000273:Adipose Tissue; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D003600:Cytosol / Q000201:enzymology; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007527:Isoenzymes / Q000032:analysis*; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D007527:Isoenzymes; D011493:Protein Kinase C; D005947:Glucose