title: Long-term pioglitazone treatment augments insulin sensitivity and PKC-epsilon and PKC-theta activation in skeletal muscles in sucrose fed rats.
abstract: 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-epsilon and -theta 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 insulin-stimulated 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 micromol/g, P<0.005). Pioglitazone-treated rats exhibited significantly increased membrane/total (cytosolic plus membrane) ratio of both PKC-epsilon and PKC-theta 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-epsilon and -theta isoforms in spite of increased lipid concentration in skeletal muscles.
authors.affiliation: Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: I
authors.initials: I
authors.lastname: Marková
authors.forename: V
authors.initials: V
authors.lastname: Zídek
authors.forename: A
authors.initials: A
authors.lastname: Musilová
authors.forename: M
authors.initials: M
authors.lastname: Šimáková
authors.forename: P
authors.initials: P
authors.lastname: Mlejnek
authors.forename: L
authors.initials: L
authors.lastname: Kazdová
authors.forename: M
authors.initials: M
authors.lastname: Pravenec
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001786:Blood Glucose / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D019422:Dietary Sucrose / Q000008:administration & dosage* / Q000378:metabolism; D004195:Disease Models, Animal; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D000077205:Pioglitazone; D011493:Protein Kinase C / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D021381:Protein Transport; D051381:Rats; D011918:Rats, Inbred SHR; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens; D019422:Dietary Sucrose; D007004:Hypoglycemic Agents; D007328:Insulin; D007527:Isoenzymes; D045162:Thiazolidinediones; D014280:Triglycerides; D006003:Glycogen; C497257:Prkce protein, rat; C489591:Prkcq protein, rat; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D000074121:Protein Kinase C-theta; D000077205:Pioglitazone