title: Pioglitazone-induced increase of insulin sensitivity in the muscles of the obese Zucker fa/fa rat cannot be explained by local adipocyte differentiation.
abstract: Thiazolidinediones are potent antidiabetic compounds, which act by enhancing peripheral insulin sensitivity. They are also activators of the peroxisome proliferator activated receptor gamma in adipose tissue. Pioglitazone induces in vivo adipocyte differentiation in the obese Zucker fa/fa rat and hence the capacity of adipose tissue to utilize glucose. Nevertheless, muscles are the major site for insulin-mediated glucose disposal. The increase of muscle glucose utilization under thiazolidinedione treatment could be secondary to local adipose tissue differentiation. This possibility is supported by the fact that a thiazolidinedione-induced myoblast conversion into adipocytes has been described in vitro. To address this problem, we have studied the in vivo effect of a pioglitazone treatment on insulin-induced glucose utilization and the expression of genes exclusively expressed in mature adipocytes in three muscles differing by their fibre composition in Zucker (fa/fa) rats. Whereas pioglitazone treatment increased insulin-stimulated glucose utilization to the same extent in all muscle types, an adipocyte differentiation was only present in the oxidative muscle, the soleus. Soleus muscle was also the only one in which the presence of genes specific for adipose tissue could be detected before the pioglitazone treatment. There was no detectable expression of adipocyte specific genes in the extensor digitorum longus or in the epitrochlearis muscles before or after the drug treatment. We conclude that pioglitazone effects on muscle glucose metabolism cannot be due to a local adipocyte differentiation, and that the conversion of myoblasts into adipocytes under thiazolidinedione stimulation observed in vitro is, if it exists, a marginal phenomenon in vivo.
authors.affiliation: U465 INSERM, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Hallakou
authors.forename: F
authors.initials: F
authors.lastname: Foufelle
authors.forename: L
authors.initials: L
authors.lastname: Doaré
authors.forename: M
authors.initials: M
authors.lastname: Kergoat
authors.forename: P
authors.initials: P
authors.lastname: Ferré
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D019014:fas Receptor / Q000235:genetics
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D019014:fas Receptor; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose; D000077205:Pioglitazone