EFFECTS OF INSULIN ON HEMODYNAMICS AND METABOLISM IN HUMAN FOREARM

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 mumol.min-1.dl-1 forearm vol), beta-hydroxybutyrate (0.267 +/- 0.130 mumol.min-1.dl-1), and O2 (9.96 +/- 1.02 mumol.min-1.dl-1) and released lactate (0.284 +/- 0.098 mumol.min-1.dl-1), glycerol (0.029 +/- 0.012 mumol.min-1.dl-1), citrate (0.091 +/- 0.030 mumol.min-1.dl-1), alanine (0.184 +/- 0.044 mumol.min-1.dl-1), CO2 (7.36 +/- 0.97 mumol.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 microU/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 mumol.min-1.dl-1 forearm vol, P less than 0.001), lactate and pyruvate release (to 0.710 +/- 0.093 and 0.032 +/- 0.016 mumol.min-1.dl-1 forearm vol, respectively; P less than 0.01 for both), potassium uptake (0.76 +/- 0.22 mueq.min-1.dl-1, P less than 0.001), and free fatty acid uptake (0.123 +/- 0.041 mumol.min-1.dl-1 forearm vol, P less than 0.05); glycerol balance switched to a net uptake (P less than 0.001), alanine release was restrained by 33% (P less than 0.05), and beta-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 less than 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 less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)