It has been suggested that thiazolidinediones (TZDs) ameliorate insulin resistance in muscle tissue by suppressing muscle lipid storage and the activity of novel protein kinase C (nPKC) isoforms. To test this hypothesis, we analyzed long-term metabolic effects of pioglitazone and the activation of nPKC-? and -? isoforms in an animal model of the metabolic syndrome, the spontaneously hypertensive rat (a congenic SHR strain with wild type Cd36 gene) fed a diet with 60 % sucrose from the age of 4 to 8 months. Compared to untreated controls, pioglitazone treatment was associated with significantly increased basal (809±36 vs 527±47 nmol glucose/g/2h, P<0.005) and insulinstimulated glycogenesis (1321±62 vs 749±60 nmol glucose/g/2h, P<0.0001) in isolated gastrocnemius muscles despite increased concentrations of muscle triglycerides (3.83±0.33 vs 2.25±0.12 µmol/g, P<0.005). Pioglitazone-treated rats exhibited significantly increased membrane/total (cytosolic plus membrane) ratio of both PKC-? and PKC-? isoforms compared to untreated controls. These results suggest that amelioration of insulin resistance after long-term pioglitazone treatment is associated with increased activation of PKC-? and -? isoforms in spite of increased lipid concentration in skeletal muscles.

Inst Physiol Acad Sci Czech Rep Prague

Institute for Experimental and Clinical Medicine Prague Czech Republic

Institute of Physiology Academy of Sciences of the Czech Republic Prague Czech Republic

Citace poskytuje Crossref.org

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