Bariatric surgery relieves type 2 diabetes and modulates inflammatory factors and coronary endothelium eNOS/iNOS expression in db/db mice

Overexpression of endothelial nitric oxide synthetase (eNOS)/inducible nitric oxide synthase (iNOS) and inhibition of inflammatory factors can improve vascular function. We hypothesized that bariatric (gastric bypass) surgery could inhibit inflammatory factors and improve the eNOS/iNOS expression of coronary arterioles in the db/db mice. The animals were randomly allocated to the following groups: sham-operated lean mice, lean mice that underwent surgery, sham-operated db/db mice, and db/db mice that underwent surgery (5, 10, 20, and 30 days post-operation). The plasma levels of adiponectin, ghrelin, and IL-6, as well as the protein expression of eNOS/iNOS in coronary arterioles were measured with Western blot. Bariatric surgery decreased body mass and blood glucose levels in db/db mice. Ghrelin receptor and GHS-R1a expression in the hypothalamus were increased in db/db mice, but surgery attenuated GHS-R1a expression. Bariatric surgery elevated plasma concentration and protein expression of adiponectin and ghrelin, and attenuated plasma concentration and protein expression of IL-6. Coronary protein expression of eNOS and SOD2 was lower in the sham-operated db/db mice, and bariatric surgery increased eNOS and SOD2 expression. Gastric bypass surgery upregulates ghrelin and adiponectin expression, and decreases IL-6 expression, which might induce up-regulation of eNOS and SOD2, and down-regulation of iNOS. These interactions could counteract the endothelium dysfunction in type 2 diabetes mellitus.