Effects of Insulin on Hemodynamics and Metabolism in Human Forearm

Abstract

We investigated the vascular response (blood flow and resting vascular resistance) and the metabolic response (exchange of metabolites and respiratory gases) to local insulin administration in the forearms of healthy young volunteers with the use of the perfused-forearm technique. In the postabsorptive state, the deep tissues of the forearm (mostly skeletal muscle) took up glucose (mean ± SE 1.09 ± 0.17 μmol · min−1 · dl−1 forearm vol), β-hydroxybutyrate (0.267 ± 0.130 μmol · min−1 · dl1), and O2 (9.96 ± 1.02 μmol · min−1 · dl−1) and released lactate (0.284 ± 0.098 μmol · min−1 · dl−1), glycerol (0.029 ± 0.012 μmol · min−1 · dl−1), citrate (0.091 ± 0.030 μmol · min−1 · dl1), alanine (0.184 ± 0.044 μmol · min−1 · dl−1), Co2 (7.36 ± 0.97 μmol · min−1 · dl−1), and protons (12.1 ±1.4 pmol · min−1 · dl−1). Forearm blood flow (by venous occlusion plethysmography) was 2.95 ± 0.18 ml · min−1 · dl−1, and intra-arterial systolic/diastolic blood pressure was 116 ± 3/76 ± 2 mmHg. Local indirect calorimetry indicated dominance of fat as the oxidative substrate (RQ 0.76 ± 0.09) and an energy expenditure rate of 1.03 ± 0.11 cal · min−1 · dl−1 forearm vol. One hundred minutes of intra-arterial insulin infusion (deep venous plasma insulin concn of 125 ± 11 μU/ml) had no detectable effect on forearm blood flow, resting forearm vascular resistance, heart rate, or blood pressure. Local hyperinsulinemia significantly stimulated glucose uptake (to 4.79 ± 0.61 μmol · min−1 · dl−1 forearm vol, P <0.001), lactate and pyruvate release (to 0.710 ± 0.093 and 0.032 ± 0.016 μmol · min−1 · dl−1 forearm vol, respectively; P < 0.01 for both), potassium uptake (0.76 ± 0.22 μeq · min−1 · dl−1, P < 0.001), and free fatty acid uptake (0.123 ± 0.041 μmol · min−1 · dl−1 forearm vol, P < 0.05); glycerol balance switched to a net uptake (P < 0.001), alanine release was restrained by 33% (P < 0.05), and β-hydroxybutyrate and citrate release were unchanged. Despite these metabolic changes, local rates of substrate oxidation and energy expenditure were not altered by insulin. In contrast, forearm proton release was significantly stimulated by insulin (to 14.8 ±1.4 pmol · min−1 · dl−1 P < 0.02). Proton release was also found to be directly related to resting forearm vascular resistance independent of the effect of insulin (multiple r = 0.64, P < 0.001). We conclude that, in the deep tissues of human forearm, physiological hyperinsulinemia 1) has no acute hemodynamic action, 2) stimulates glucose uptake and restrains lipolysis but does not change the pattern of substrate oxidation, 3) exerts no thermogenic effect, and 4) promotes net extrusion of protons. The fact that, in the same district, vascular resistance bears a direct relationship to proton release suggests that resting vascular tone and skeletal muscle metabolism may be related characteristics in humans.