期刊
LIFE SCIENCES
卷 88, 期 23-24, 页码 1055-1062出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2011.04.001
关键词
Pioglitazone; PPAR-gamma; AdipoR2; AMPK
资金
- Salt Science Research Foundation [08C4]
- Kanae Foundation for Life & Soci-Medical Science
- Takeda Science Foundation
- Ministry of Education, Culture, Sports, Science, and Technology
Aims: Pioglitazone, a full peroxisome proliferator-activated receptor (PPAR)-gamma agonist, improves insulin sensitivity by increasing circulating adiponectin levels. However, the molecular mechanisms by which pioglitazone induces insulin sensitization are not fully understood. In this study, we investigated whether pioglitazone improves insulin resistance via upregulation of either 2 distinct receptors for adiponectin (AdipoR1 or AdipoR2) expression in 3T3-L1 adipocytes. Main methods: Glucose uptake was evaluated by 2-[(3)H] deoxy-glucose uptake assay in 3T3-L1 adipocytes with pioglitazone treatment. AdipoR1 and AdipoR2 mRNA expressions were analyzed by qRT-PCR. Key findings: We first confirmed that pioglitazone significantly increased insulin-induced 2-deoxyglucose (2-DOG) uptake in 3T3-L1 adipocytes. Next, we investigated the mRNA expression and regulation of AdipoR1 and AdipoR2 after treatment with pioglitazone. Interestingly, pioglitazone significantly induced AdipoR2 expression but it did not affect AdipoR1 expression. In addition, adenovirus-mediated PPAR gamma expression significantly enhanced the effects of pioglitazone on insulin-stimulated 2-DOG uptake and AdipoR2 expression in 3T3-L1 adipocytes. These data suggest that pioglitazone enhances adiponectin's autocrine and paracrine actions in 3T3-L1 adipocytes via upregulation of PPAR gamma-mediated AdipoR2 expression. Furthermore, we found that pioglitazone significantly increased AMP-activated protein kinase (AMPK) phosphorylation in insulin-stimulated 3T3-L1 adipocytes, but it did not lead to the phosphorylation of IRS-1, Akt, or protein kinase C lambda/zeta. Significance: Our results suggest that pioglitazone increases insulin sensitivity, at least partly, by PPAR gamma-AdipoR2-mediated AMPK phosphorylation in 3T3-L1 adipocytes. In conclusion, the upregulation of AdipoR2 expression may be one of the mechanisms by which pioglitazone improves insulin resistance in 3T3-L1 adipocytes. (C) 2011 Elsevier Inc. All rights reserved.
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