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

Abstract

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.

• Authors: K S Bell, C Schmitz-Peiffer, M Lim-Fraser, T J Biden, G J Cooney, E W Kraegen
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 279 Issue 5 Pg. E1196-201 (Nov 2000) ISSN: 0193-1849 [Print] United States
• PMID: 11052977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Dietary Carbohydrates
• Dietary Fats
• Insulin
• Isoenzymes
• Protein Kinase C
• Glucose

Topics

• Adipose Tissue
• Animals
• Blood Glucose (metabolism)
• Body Composition
• Cytosol (enzymology)
• Dietary Carbohydrates (administration & dosage)
• Dietary Fats (administration & dosage, pharmacology)
• Glucose (administration & dosage)
• Glucose Clamp Technique
• Insulin (blood)
• Insulin Resistance
• Isoenzymes (analysis)
• Male
• Muscle Fibers, Fast-Twitch (drug effects, enzymology, ultrastructure)
• Muscle, Skeletal (drug effects, enzymology, ultrastructure)
• Protein Kinase C (analysis)
• Rats
• Rats, Wistar