The antiketogenic effect of alanine in normal man: Evidence for an alanine-ketone body cycle

Abstract

The effect of alanine on ketone body levels, independent of hormonal changes, in normal man has been investigated. Five normal subjects were given somatostatin infusions (200 μg/hour) for 3 hr. After 1 hr alanine or isotonic saline was infused for 2 hr. With saline blood β-hydroxybutyrate and acetoacetate levels rose steadily to a peak of 0.230 ± 0.053 and 0.112 ± 0.023 mmole/l respectively. With alanine β-hydroxybutyrate and acetoacetate levels plateaued at 0.099 ± 0.020 and 0.055 ± 0.006 mmole/l respectively. Alanine levels reached nearly 1 mmole/l but a significant effect on ketone body levels was apparent at physiologic levels (<0.6 mmole/l). Plasma fatty acid and glycerol levels did not change significantly. Insulin C-peptide and glucagon levels were suppressed to a similar extent in both experiments. These results support the view that alanine suppresses ketogenesis in man by a direct hepatic effect independent of insulin and glucagon. It is suggested that this forms part of a negative feedback substrate cycle between alanine and ketone bodies.