Phenylacetate ingestion has been used to probe Krebs cycle metabolism and to augment waste
nitrogen excretion in
urea cycle disorders. Phenylalkanoic
acids, including
phenylacetate, have been proposed as potential therapeutic agents in the treatment of diabetes. They inhibit gluconeogenesis in the liver in vitro and reduce the
blood glucose concentration in diabetic rats. The effect of
sodium phenylacetate ingestion on
blood glucose and the contribution of gluconeogenesis to
glucose production have now been studied in 7 type 2 diabetic patients. The study was not designed to test whether the changes in
glucose metabolism observed in the rat could be reproduced in humans. After an overnight fast, over a period of 1 hour, 4.8 g
phenylacetate was ingested, which is the highest dose used to probe Krebs cycle metabolism.
Glucose production was measured by tracer kinetics using [6,6-(2)H2]
glucose and gluconeogenesis by the labeling of the hydrogens of
blood glucose on (2)H20 ingestion. The concentration of
phenylacetate in plasma peaked by 2 hours after its ingestion, and about 40% of the dose was excreted in 5 hours. The plasma
glucose concentration and production, and the contribution of gluconeogenesis to
glucose production, were unaffected by
phenylacetate ingestion at the highest dose used to probe Krebs cycle metabolism.