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Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents

H Singh Ahuja1, S Liu, D L Crombie

  • 1Department of Integrative Biology and Pharmacology, University of Texas Medical School, Houston, Texas 77030, USA.

Molecular Pharmacology
|March 22, 2001
PubMed

Insights

Rexinoids and thiazolidinediones (TZDs) impact metabolic control differently in diabetic rats. These findings suggest independent, tissue-specific effects of rexinoids and TZDs on glucose regulation in vivo.

Area of Science:

  • Metabolic diseases
  • Endocrinology
  • Molecular biology

Background:

  • Thiazolidinediones (TZDs) and retinoid X receptor (RXR)-selective agonists (rexinoids) are known to improve insulin sensitivity in diabetic models.
  • In vitro, TZDs activate the RXR/PPAR-gamma complex, suggesting a potential mechanism for their insulin-sensitizing effects.

Purpose of the Study:

  • To investigate whether rexinoids lower hyperglycemia by activating the RXR/PPAR-gamma heterodimer in vivo.
  • To compare the in vivo effects of a rexinoid (LG100268) and a TZD (rosiglitazone) on gene expression in key metabolic tissues.

Main Methods:

  • Zucker diabetic fatty rats (ZDFs) were treated with LG100268 (rexinoid) or rosiglitazone (TZD).
  • Gene expression analysis was performed on white adipose tissue, skeletal muscle, and liver samples.
  • Specific genes related to glucose and lipid metabolism were quantified, including TNF-alpha, GLUT4, MCPT, SCD1, and CD36.

Main Results:

  • Rosiglitazone decreased TNF-alpha and induced GLUT4, MCPT, SCD1, and CD36 in adipose tissue.
  • LG100268 increased TNF-alpha and had varied effects on other genes in adipose tissue.
  • In the liver, LG100268 increased MCPT, SCD1, and CD36, while rosiglitazone had a minimal effect.
  • Both compounds increased SCD1 and CD36 in skeletal muscle.

Conclusions:

  • Rexinoids and TZDs exhibit distinct patterns of gene induction in diabetic rats, indicating tissue-specific effects.
  • The in vivo mechanisms of action for rexinoids and TZDs in metabolic control may differ.
  • These findings suggest that rexinoids might not solely act through the RXR/PPAR-gamma heterodimer for insulin sensitization in vivo.

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