Regular Article
In VivoEffects of Pioglitazone on Uncoupling Protein-2 and -3 mRNA Levels in Skeletal Muscle of Hyperglycemic KK Mice

https://doi.org/10.1006/bbrc.1998.9479Get rights and content

Abstract

Pioglitazone is a thiazolidinedione drug (TZD) which potently and specifically stimulates peroxisome proliferator-activated receptor γ (PPAR γ) 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 muscleUCP2gene expressionin vivo.Therefore,UCP3gene expression is controlled by a different mechanism thanUCP2expression.

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    Abbreviations: BAT, brown adipose tissue; NIDDM, non-insulin dependent diabetes mellitus; PPAR, peroxisome proliferator-activated receptor; RT-PCR, reverse transcription-polymerase chain reaction; TNF-α, tumor necrosis factor-α ; TZD, thiazolidinediones; UCP, uncoupling protein; WAT, white adipose tissue

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    Corresponding author: Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltds., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585 Japan. Fax: +81-298-52-5412. E-mail:[email protected].

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