Gs. Meneilly et al., Lack of effect of sodium nitroprusside on insulin-mediated blood flow and glucose disposal in the elderly, METABOLISM, 49(3), 2000, pp. 373-378
Insulin increases skeletal muscle blood flow in healthy young subjects by a
nitric oxide (NO)-dependent mechanism. Impairment of this mechanism may co
ntribute to the insulin resistance of normal aging, a state characterized b
y reduced endothelial production of NO, an attenuated effect of insulin on
skeletal muscle blood flow, and resistance to insulin-mediated glucose upta
ke (IMGU). We tested the hypothesis that the NO donor sodium nitroprusside
(SNP) would augment insulin-mediated vasodilation and thus increase IMGU in
healthy elderly subjects. Experiments were performed with young (n = 9; ag
e, 25 +/- 1 years; body mass index [BMI], 24 +/- 1 kg/m(2)) and old (n = 10
; age, 78 +/- 2 years: BMI, 25 +/- 1 kg/m(2)) healthy subjects. Each group
underwent two studies in random order. In one study (control), insulin was
infused using the euglycemic clamp protocol for 240 minutes at a rate of 40
mU/m(2)/min (young) and 34 mU/m(2)/min (old). In the other study (SNP), SN
P was coinfused with insulin from 120 to 240 minutes. At regular intervals
in each study, blood samples were obtained and calf blood flow was measured
using venous occlusion plethysmography. Glucose and insulin values were si
milar in control and SNP studies in both age groups. In the young, SNP had
no effect on blood flow to the calf, but its action in calf resistance vess
els augmented insulin-mediated vasodilation, since incremental calf vascula
r conductance was greater during SNP infusion (control v SNP, 0.027 +/- 0.0
02 v 0.040 +/- 0.008 mL/100 mL/min/mm Hg, P < .0001). However, SNP had no e
ffect on insulin-mediated glucose disposal. In the elderly, SNP reduced the
blood flow to the calf, but this was countered by its effect on calf resis
tance vessels such that vascular conductance was unaffected (control v SNP,
0.012 +/- 0.003 v 0.011 +/- 0.003 mL/100 mL/min/mm Hg, P = nonsignificant
[NS]). Steady-state (180 to 240 minutes) glucose disposal (control v SNP, 7
.47 +/- 0.47 v 6.54 +/- 0.56 mg/kg/min, P < .01) rates were significantly l
ower during SNP infusion. In summary, systemic infusion of SNP did not incr
ease insulin-mediated glucose disposal in either young or old subjects. Thu
s, the present findings do not support the concept that increasing NO avail
ability will enhance glucose disposal in either age group. However, because
the incremental increases in IMGU during SNP infusion paralleled the chang
es in blood supply to the calf rather than calf vascular conductance, any p
otential benefits on NO delivery in elderly subjects may have been offset b
y the direct or reflex effects of systemic hypotension. Other stimuli to NO
production that do not cause hypotension must be tested before this therap
eutic strategy can be considered as a potential means for enhancing the met
abolic actions of insulin in the elderly. Copyright (C) 2000 by W.B. Saunde
rs Company.