Type 2 diabetes is associated with metabolic and physiologic abnormalities, such as elevated plasma glucose, dyslipidemia, and hypertension. Although insulin resistance is a major contributor to diabetes pathogenesis, chronic inflammation contributes to many of the physiological complications. The observation that thiazolidinediones ameliorate insulin resistance demonstrates that their target, peroxisome proliferator-activated receptor (PPARγ), has a major role in the etiology of type 2 diabetes. Recent work has shown that a potent phosphodiesterase type III inhibitor, cilostazol [6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone], activates PPARγ. Cilostazol is used clinically as an anti-platelet drug. In this issue, Park et al., describe the effect of cilostazol on insulin resistance and inflammation in the experimental db/db mouse model of type 2 diabetes. The authors found that cilostazol attenuated several key metabolic abnormalities found in the db/db mice. There was a reduction in glucose, triglyceride, insulin, and resistin levels and an elevation of adiponectin levels in plasma. Cilostazol also increased mRNA expression for adiponectin, adipocyte fatty acid-binding protein, and fatty acid transport protein in the adipose tissue and inhibited inflammation, as measured from decreases in proinflammatory markers, such as superoxide, tumor necrosis factor-α, and vascular cell adhesion molecule-1 in the carotid artery. It was also found that cilostazol activated PPARγ transcription in 3T3-L1 fibroblasts in a mechanism involving phosphatidylinositol 3-kinase/Akt signaling. It is concluded that cilostazol might ameliorate the inflammatory component of type 2 diabetes along with improvement of insulin sensitivity.
See article at J Pharmacol Exp Ther 2009, 329:571-579.
- The American Society for Pharmacology and Experimental Therapeutics