Somatomedin-A inhibits glucagon-stimulated hepatic gluconeogenesis

Somatomedin/insulin-like growth factors have been noted to produce insulin-like actions on the liver that include the ability to inhibit the formation of glucagon-stimulated but not basal c-AMP production. This raises the possibility that these compounds may also be able to inhibit glucagon-stimulated hepatic gluconeogenesis. The purpose of this study was to determine the effects of varying concentrations of somatomedin-A on glucagon-stimulated gluconeogenesis in isolated perfused rat liver. The infusion of glucagon increased the rate of gluconeogenesis from 0.0038 +/- 0.001 to 0.042 +/- 0.007 microM 14C-glucose made from 14C-alanine per min. This action of glucagon was reduced to 22% of its maximum by the coinfusion of 1 microU/ml of SM-A and completely eliminated by the coinfusion of 100 microU/ml of SM-A. Somatomedin alone did not alter the basal rate of gluconeogenesis. The decrease in the release of 14C glucose from livers that had been stimulated by glucagon could not be attributed to increased glycogenolysis. Thus, it appears that the reduction in 14C release represents SM-A mediated reduction in glucagon-stimulated gluconeogenesis.