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$PPAR{\gamma}$ Agonist Beyond Glucose Lowering Effect

  • Sugawara, Akira (Department of Advanced Biological Sciences for Regeneration, Tohoku University Graduate School of Medicine) ;
  • Uruno, Akira (Department of Medical Biochemistry, Tohoku University Graduate School of Medicine) ;
  • Kudo, Masataka (Department of Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine) ;
  • Matsuda, Ken (Department of Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine) ;
  • Yang, Chul-Woo (Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine) ;
  • Ito, Sadayoshi (Department of Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine)
  • Published : 2011.03.01

Abstract

The nuclear hormone receptor $PPAR{\gamma}$ is activated by several agonists, including members of the thiazolidinedione group of insulin sensitizers. Pleiotropic beneficial effects of these agonists, independent of their blood glucose-lowering effects, have recently been demonstrated in the vasculature. $PPAR{\gamma}$ agonists have been shown to lower blood pressure in animals and humans, perhaps by suppressing the renin-angiotensin (Ang)-aldosterone system (RAAS), including the inhibition of Ang II type 1 receptor expression, Ang-II-mediated signaling pathways, and Ang-II-induced adrenal aldosterone synthesis/secretion. $PPAR{\gamma}$ agonists also inhibit the progression of atherosclerosis in animals and humans, possibly through a pathway involving the suppression of RAAS and the thromboxane $A_2$ system, as well as the protection of endothelial function. Moreover, $PPAR{\gamma}$-agonist-mediated renal protection, especially the reduction of albuminuria, has been observed in diabetic nephropathy, including animal models of the disease, and in non-diabetic renal dysfunction. The renal protective activities may reflect, at least in part, the ability of $PPAR{\gamma}$ agonists to lower blood pressure, protect endothelial function, and cause vasodilation of the glomerular efferent arterioles. Additionally, anti-neoplastic effects of $PPAR{\gamma}$ agonists have recently been described. Based on the multiple therapeutic actions of $PPAR{\gamma}$ agonists, they will no doubt lead to novel approaches in the treatment of lifestyle-related and other diseases.

Keywords

References

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