Effect of physiological elevation of plasma growth hormone levels on ketone body kinetics and lipolysis in normal and acutely insulin-deficient man

Abstract

The effect of physiological elevation of growth hormone levels on ketone body kinetics was determined using a 14C-ketone body tracer technique in normal and acutely insulin-deficient man. Changes of ketone body production and metabolic clearance rates during growth hormone infusion (plasma levels of approximately 25 micrograms/1) were measured during basal conditions and during heparin-induced elevation of non-esterified fatty acid levels. Growth hormone administration to six subjects fasted overnight resulted in an increase in ketone body production which exceeded that observed in nine control subjects (5.5 +/- 0.5 versus 3.1 +/- 0.1 mumol X kg-1 X min-1, p less than 0.025) after elevation of plasma non-esterified fatty acids. Growth hormone infusion increased glycerol and non-esterified fatty acid concentrations indicating enhanced lipolysis. During somatostatin-induced acute insulin deficiency (n = 7), growth hormone enhanced the increase in total ketone body production observed in six subjects receiving somatostatin alone (8.4 +/- 0.8 versus 4.1 +/- 0.7 mumol X kg-1 X min-1, p less than 0.01). Total ketone body metabolic clearance decreased by 50% during somatostatin and remained uninfluenced by growth hormone. Non-esterified fatty acids and glycerol levels increased during somatostatin, and growth hormone failed to alter non-esterified fatty acid levels significantly. The results demonstrate a stimulatory effect of high physiological growth hormone levels on ketogenesis which is largely explained by an enhancement of lipolysis and thus increase in substrate supply for ketogenesis. Growth hormone administration during acute insulin deficiency enhanced ketogenesis in the absence of alterations in plasma non-esterified fatty acid levels, suggesting a direct hepatic ketogenic effect.