Long-term pioglitazone treatment augments insulin sensitivity and PKC-epsilon and PKC-theta activation in skeletal muscles in sucrose fed rats.
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.
Marková
I
I
Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
Zídek
V
V
Musilová
A
A
Šimáková
M
M
Mlejnek
P
P
Kazdová
L
L
Pravenec
M
M
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
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