Failure of glucagon to stimulate ketone body production during acute insulin deficiency or insulin replacement in man.

To assess the role of glucagon and insulin in the acute regulation of ketone body kinetics in man, somatostatin was administered with various combinations of these hormones by replacement infusions in groups of six to seven normal subjects. Somatostatin-induced insulin and glucagon deficiency produced a threefold increase in total ketone body concentrations within 2 h. This increase was the combined result of enhanced production (71%), and decreased metabolic clearance (32%), as determined by 14C-acetoacetate infusions. An associated elevation of non-esterified fatty acids (66%) and glycerol levels occurred. Glucagon replacement (2 ng . kg-1 . min-1) during insulin deficiency failed to enhance ketogenesis or lipolysis but lowered the beta-hydroxybutyrate/acetoacetate concentration ratios. Hyperglycaemia, observed during glucagon administration and insulin deficiency, did not diminish ketone body production or lipolysis. In contrast, insulin replacement (150 microunits . kg-1 . min-1) diminished lipolysis, lowered ketone production, and elevated the metabolic clearance rate of ketone bodies. Glucagon infusions (2 and 4 ng . kg-1 . min-1) during somatostatin and insulin replacement did not accelerate ketone body production or raise non-esterified fatty acid levels, but produced a dose-dependent elevation of blood glucose levels. The results suggest that glucagon is not an important ketogenic hormone under the conditions studied.