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Aim . To investigate the combination effects and mechanisms of valsartan (angiotensin II type 1 receptor blocker) and LAF237 (DPP-IV inhibitor) on prevention against oxidative stress and inflammation injury in db/db mice aorta.  Methods . Db/db mice ( n  = 40) were randomized to receive valsartan, LAF237, valsartan plus LAF237, or saline. Oxidative stress and inflammatory reaction in diabetic mice aorta were examined.  Results . Valsartan or LAF237 pretreatment significantly increased plasma GLP-1 expression, reduced apoptosis of endothelial cells isolated from diabetic mice aorta. The expression of NAD(P)H oxidase subunits also significantly decreased resulting in decreased superoxide production and ICAM-1 (fold change: valsartan : 7.5 ± 0.7,  P  < 0.05; LAF237: 10.2 ± 1.7,  P  < 0.05), VCAM-1 (fold change: valsartan : 5.2 ± 1.2,  P  < 0.05; LAF237: 4.8 ± 0.6,  P  < 0.05), and MCP-1 (fold change: valsartan: 3.2 ± 0.6, LAF237: 4.7 ± 0.8;  P  < 0.05) expression. Moreover, the combination treatment with valsartan and LAF237 resulted in a more significant increase of GLP-1 expression. The decrease of the vascular oxidative stress and inflammation reaction was also higher than monotherapy with valsartan or LAF237.  Conclusion . These data indicated that combination treatment with LAF237 and valsartan acts in a synergistic manner on vascular oxidative stress and inflammation in type 2 diabetic mice.

experimental diabetes research

The Synergistic Effect of Valsartan and LAF237 [(S)-1-[(3-Hydroxy-1-Adamantyl)Ammo]acetyl-2-Cyanopyrrolidine] on Vascular Oxidative Stress and Inflammation in Type 2 Diabetic Mice