DISSOCIATION BETWEEN INSULIN SENSITIVITY OF GLUCOSE-UPTAKE AND ENDOTHELIAL FUNCTION IN NORMAL SUBJECTS

Insulin increases limb blood flow in a time- and dose-dependent manner . This effect can be blocked by inhibiting nitric oxide synthesis. The se data raise the possibility that insulin resistance is associated wi th endothelial dysfunction. To examine whether endothelial function an d insulin sensitivity are interrelated we quantitated in vivo insulin- stimulated rates of whole body and forearm glucose uptake at a physiol ogical insulin concentration (euglycaemic hyperinsulinaemic clamp, 1 m U . kg(-1). min(-1) insulin infusion for 2 h) and on another occasion, in vivo endothelial function (blood flow response to intrabrachial in fusions of sodium nitroprusside, acetylcholine, and N-monomethyl-L-arg inine) in 30 normal male subjects. Subjects were divided into an insul in-resistant (IR) and an insulin-sensitive (IS) group based on the med ian rate of whole body glucose uptake (31 +/- 2 vs 48 +/- 1 mu mol . k g(-1). min(-1), p < 0.001). The IR and IS groups were matched for age, but the IR group had a slightly higher body mass index, percentage of body fat and blood pressure compared to the IS group. The IR group al so had diminished insulin-stimulated glucose extraction (p < 0.05) com pared to the IS group, while basal and insulin-stimulated forearm bloo d now rates were identical. There was no difference between the IR and IS groups in the forearm blood flow response to endothelium-dependent (acetylcholine and N-monomethyl-L-arginine) or -independent (sodium n itroprusside) vasoactive drugs. In conclusion, the ability of insulin to stimulate glucose uptake at physiological insulin concentrations an d endothelium-dependent vasodilatation are distinct phenomena and do n ot necessarily coexist.