Abstract
Background: glycemia disorders are a strong predictor of mortality in ST-Elevation Myocardial Infarction (STEMI) patients. Disruption in nitric oxide (NO) production is associated with insulin-resistant states. We evaluated whether NO production in carriers of a defective allele of the neuronal nitric oxide synthase (nNOS or NOS1), whose in vivo expression is reduced by up to 50%, might influence the insulin response during acute phase of STEMI. Methods and Results: Consecutive patients with STEMI (n = 354) underwent clinical evaluations and genotyping for the promoter variation rs41279104. Blood tests were performed at admission (D1) and after five days (D5) of in-hospital follow up, with the disposition index assessed in the period. Flow-mediated dilation (FMD) was assessed by reactive hyperemia on the 30th day. Homozygotes for the defective allele (A) showed lower glycemia and insulin sensitivity at D1 while showing the highest b-cells function and no changes in the circulating NO pool, what is compatible with hyperresponsive b-cells to counteract the inherent glucose-resistant state of AA patients. At D5, glycemic scores shifted to indicate greater insulin sensitivity among A homozygotes, paralleled by a slight yet poor increase in NO bioavailability than that among G carriers. All in all, defective homozygotes showed greater insulin resistance expressed by the disposition index at admission, which was compensated 5 days after STEMI even though FMD of A carriers was lower compared to G homozygotes. Conclusion: a defective nNOS allele seems to elicit endocrine adaptation and to associate with insulin resistance during the acute phase of STEMI.
Hepatic nitric oxide synthase 1 adaptor protein regulates glucose homeostasis and hepatic insulin sensitivity in obese mice depending on its PDZ binding domain
