Forearm nitric oxide balance, vascular relaxation, and glucose metabolism in NIDDM patients.
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.
Avogaro
A
A
Department of Clinical and Experimental Medicine, University of Padua, Italy.
Piarulli
F
F
Valerio
A
A
Miola
M
M
Calveri
M
M
Pavan
P
P
Vicini
P
P
Cobelli
C
C
Tiengo
A
A
Calò
L
L
Del Prato
S
S
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D001824:Body Constitution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005542:Forearm / Q000098:blood supply*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009569:Nitric Oxide / Q000097:blood* / Q000378:metabolism; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D005947:Glucose; D000109:Acetylcholine