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Biochem Biophys Res Commun. 1998 Oct 9;251(1):374-8.

In vivo effects of pioglitazone on uncoupling protein-2 and -3 mRNA levels in skeletal muscle of hyperglycemic KK mice.

Author information

1
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Tsukuba, Japan. simokawa@yamanouchi.co.jp

Abstract

Pioglitazone is a thiazolidinedione drug (TZD) which potently and specifically 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 uncoupling protein-2 and -3 mRNA levels in response to pioglitazone treatment 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 treatment, UCP2 mRNA levels increased to 185% of normal untreated control levels in soleus muscle. In contrast, UCP3 mRNA levels significantly decreased, 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 catabolism by direct upregulation of muscle UCP2 gene expression in vivo. Therefore, UCP3 gene expression is controlled by a different mechanism than UCP2 expression.

PMID:
9790963
DOI:
10.1006/bbrc.1998.9479
[Indexed for MEDLINE]

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