T. Shimokawa et al., IN-VIVO EFFECTS OF PIOGLITAZONE ON UNCOUPLING PROTEIN-2 AND PROTEIN-3MESSENGER-RNA LEVELS IN SKELETAL-MUSCLE OF HYPERGLYCEMIC KK MICE, Biochemical and biophysical research communications (Print), 251(1), 1998, pp. 374-378
Pioglitazone is a thiazolidinedione drug (TZD) which potently and spec
ifically stimulates peroxisome proliferator-activated receptor gamma (
PPAR gamma) and sensitizes cells to insulin. Since TZDs are thought to
increase energy expenditure, changes in mitochondrial thermogenesis u
ncoupling protein-2 and -3 mRNA levels in response to pioglitazone tre
atment were measured in mouse skeletal muscle. Normally hyperglycemic
and hyperinsulinemic KK/Ta mice were given pioglitazone for 2 weeks to
treat this non-insulin dependent diabetes-like condition. During trea
tment, UCP2 mRNA levels increased to 185% of normal untreated control
levels in soleus muscle. In contrast, UCP3 mRNA levels significantly d
ecreased, up to 67% of normal untreated control levels. Interestingly,
UCP3 mRNA levels correlated quite strongly with blood glucose levels,
with r = 0.82 for gastrocnemius tissue and r = 0.92 for soleus tissue
. These results may indicate that pioglitazone increases glucose catab
olism by direct upregulation of muscle UCP2 gene expression in vivo. T
herefore, UCP3 gene expression is controlled by a different mechanism
than UCP2 expression, (C) 1998 Academic Press.