Forearm Nitric Oxide Balance, Vascular Relaxation, and Glucose Metabolism in NIDDM Patients

Abstract

Endothelium-dependent and -independent vascular responses were assessed in 10 NIDDM patients and 6 normal subjects with no evidence of atherosclerotic disease. Changes in forearm blood flow and arteriovenous (AV) serum nitrite/nitrate (NO2-/NO3-) concentrations were measured in response to intra-arterial infusion of acetylcholine (ACh) (7.5, 15, 30 microg/min, endothelium-dependent response) and sodium nitroprusside (SNP) (0.3, 3, 10 microg/min, endothelium-independent response). Insulin sensitivity (determined by minimal model intravenous glucose tolerance test) was lower in NIDDM patients (0.82 +/- 0.20 vs. 2.97 +/- 0.29 10(4) min x microU(-1) x ml(-1); P < 0.01). Baseline forearm blood flow (4.8 +/- 0.3 vs. 4.4 +/- 0.3 ml x 100 ml(-1) tissue x min(-1); NS), mean blood pressure (100 +/- 4 vs. 92 +/- 4 mmHg; NS), and vascular resistance (21 +/- 1 vs. 21 +/- 1 units; NS), as well as their increments during ACh and SNP, infusion were similar in both groups. No difference existed in baseline NO2-/NO3- concentrations (4.09 +/- 0.33 [NIDDM patients] vs. 5.00 +/- 0.48 micromol/l [control subjects]; NS), their forearm net balance (0.31 +/- 0.08 [NIDDM patients] vs. 0.26 +/- 0.08 micromol/l x 100 ml(-1) tissue x min(-1); NS), and baseline forearm glucose uptake. During ACh infusion, both NO2- and NO3- concentrations and net balance significantly increased in both groups, whereas glucose uptake increased only in control subjects. When data from NIDDM and control groups were pooled together, a correlation was found between the forearm AV NO2- and NO3- differences and blood flow (r = 0.494, P = 0.024). On the contrary, no correlation was evident between NO2- and NO3- concentrations or net balance and insulin sensitivity. In summary, 1) no difference existed in basal and ACh-stimulated NO generation and endothelium-dependent relaxation between uncomplicated NIDDM patients and control subjects; 2) in both NIDDM and control groups, forearm NO2- and NO3- net balance following ACh stimulation was related to changes in the forearm blood flow; and 3) ACh-induced increase in forearm blood flow was associated with an increase in glucose uptake only in control subjects but not in NIDDM patients. In conclusion, our results argue against a role of impaired NO generation and blood flow regulation in determining the insulin resistance of uncomplicated NIDDM patients; rather, it supports an independent insulin regulation of hemodynamic and metabolic effects.

NADPH diaphorase activity in the rat retina during the early stages of experimental diabetes

“…In contrast to the above-mentioned reports, the endothelial cells of the mesenteric arteries in rats with prolonged diabetes were found to release normal levels of vasodilator substances, and the arteries were found to respond normally to exogenous application of NO [17]. Human studies also yielded conflicting results; some showed impaired endothelium-derived NO activity with normal response to exogenous NO [49], whereas others reported that both tests for NO-vascular interaction were reduced [6,51] or normal [2,44].…”

Impairment of nitric oxide-mediated relaxations in anaesthetized autoperfused streptozotocin-induced diabetic rats

“…Enhancement of nitrite/nitrate baseline plasma levels has been described in streptozotocin-induced diabetic rats (Goor et al 1996), while no differences from control have been reported in diabetic patients (Avogaro et al 1997). Under the present experimental conditions, even in the group of untreated diabetic rats the increase of plasma concentration of nitrites/nitrates was not significant.…”

The markers of inflammation and endothelial dysfunction in correlation with glycated haemoglobin are present in type 2 diabetes mellitus patients but not in their relatives

“…The endothelium dependent blood-flow responses have been impaired in diabetic patients in most, although not in all, studies [17,29,[39][40][41]. Reponses to sodium nitroprusside have been subnormal in many, but not in all, reports [17,41,42].…”

“…Some drugs used frequently in diabetic patients, such as estatins, fibrates, angiotensin receptor blockers, rosiglitazone, repaglinide and metformin could influence the concentrations of some of these factors [35][36][37][38][39][40][41]; this fact is a limitation of our study because eight patients were under treatment with hypoglycemic agents.…”