Effects of plasma amino acid and hormone levels on renal hemodynamics in humans

The effect of plasma amino acid and hormone (insulin, glucagon, and growth hormone) levels on renal hemodynamics was studied in 18 healthy subjects. The following four protocols were employed: study 1, a balanced amino acid solution was infused for 3 h to increase plasma amino acid concentrations two to three times base line; study 2, the same amino acid solution was infused with somatostatin (SRIF) and infusions of insulin, glucagon, and growth hormone were concomitantly administered to replace the time sequence of increase in peripheral concentrations of these hormones as observed during study 1; study 3, the same amino acid infusion was administered with SRIF plus infusions of insulin, glucagon, and growth hormone to maintain plasma hormone concentrations constant at the basal level; study 4, SRIF was infused with insulin, glucagon, and growth hormone to reproduce the time sequence of increase of these hormones as observed in study 1; amino acids were not infused in this study. During study 1, glomerular filtration rate (GFR) and renal plasma flow (RPF) rose by 19 and 21%, respectively. During study 2 both the time sequence of and magnitude of rise in GFR and in RPF were similar to the changes observed during study 1. In studies 3 and 4 neither RPF and GFR changed significantly from base line. These results indicate that 1) hyperaminoacidemia stimulates insulin/glucagon/growth hormone secretion and causes a modest rise in GFR and RPF; and 2) if hyperaminoacidemia is created while maintaining basal hormone levels constant or if plasma insulin/glucagon/growth hormone levels are increased while maintaining the plasma amino acid concentration at basal levels, neither RPF nor GFR rise. We conclude that the renal hemodynamic response following amino acid infusion is dependent on the release of some factor whose release is inhibited by somatostatin and restored by combined insulin/glucagon/growth hormone replacement

Hyperglucagonemia and insulin-mediated glucose metabolism

The effect of chronic physiologic hyperglucagonemia on basal and insulin-mediated glucose metabolism was evaluated in normal subjects, using the euglycemic insulin clamp technique (+50, +100, and +500 microU/ml). After glucagon infusion fasting glucose increased from 76 +/- 4 to 93 +/- 2 mg/dl and hepatic glucose production (HGP) rose from 1.96 +/- 0.08 to 2.25 +/- 0.08 mg/kg X min (P less than 0.001). Basal glucose oxidation after glucagon increased (P less than 0.05) and correlated inversely with decreased free fatty acid concentrations (r = -0.94; P less than 0.01) and decreased lipid oxidation (r = -0.75; P less than 0.01). Suppression of HGP and stimulation of total glucose disposal were impaired at each insulin step after glucagon (P less than 0.05-0.01). The reduction in insulin-mediated glucose uptake was entirely due to diminished non-oxidative glucose utilization. Glucagon infusion also caused a decrease in basal lipid oxidation and an enhanced ability of insulin to inhibit lipid oxidation and augment lipid synthesis. These results suggest that hyperglucagonemia may contribute to the disturbances in glucose and lipid metabolism in some diabetic patients