Down regulation of peroxisome proliferator-activated receptorγ expression by inflammatory cytokines and its reversal by thiazolidinediones

T. Tanaka, H. Itoh, K. Doi, Y. Fukunaga, K. Hosoda, M. Shintani, J. Yamashita, T. H. Chun, M. Inoue, K. Masatsugu, N. Sawada, T. Saito, G. Inoue, H. Nishimura, Y. Yoshimasa, K. Nakao

研究成果: Article査読

110 被引用数 (Scopus)

抄録

Aims/hypothesis. Previous studies show that inflammatory cytokines play a part in the development of insulin resistance. Thiazolidinediones were developed as insulin-sensitizing drugs and are ligands for the peroxisome proliferator-activated receptorγ (PPARγ). We hypothesized that the anti- diabetic mechanism of thiazolidinediones depends on the quantity of PPARγ in the insulin resistant state in which inflammatory cytokines play a part. Methods. We isolated rat PPARγ1 and γ2 cDNAs and examined effects of various cytokines and thiazolidinediones on PPARγ mRNA expression in rat mature adipocytes. Results. Various inflammatory cytokines, such as tumour necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6 and leukaemia inhibitory factor decreased PPARγ mRNA expression. In addition, hydrogen peroxide, lysophosphatidylcholine or phorbol 12-myristate 13- acetate also decreased the expression of PPARγ. The suppression of PPARγ mRNA expression caused by 10 nmol/l of TNF-α was reversed 60% and 55% by treatment with 10-4 mol/l of troglitazone and 10-4 mol/l of pioglitazone, respectively. The suppression of glucose transporter 4 mRNA expression caused by TNF-α was also reversed by thiazolidinediones. Associated with the change of PPARγ mRNA expression, troglitazone improved glucose uptake suppressed by TNF-α. Conclusion/interpretation. Our study suggests that inflammatory cytokines could be factors that regulate PPARγ expression for possible modulation of insulin resistance. In addition, we speculate that the regulation of PPARγ mRNA expression may contribute to the anti-diabetic mechanism of thiazolidinediones.

本文言語English
ページ(範囲)702-710
ページ数9
ジャーナルDiabetologia
42
6
DOI
出版ステータスPublished - 1999
外部発表はい

ASJC Scopus subject areas

  • 内科学
  • 内分泌学、糖尿病および代謝内科学

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