Modulation of fatty acid metabolism by glucagon in man. I. Effects in normal subjects

This investigation was designed to examine the contribution of glucagon to the regulation of free fatty acid (FFA) metabolism in man. The acute effects of exogenous glucagon upon the concentration of plasma FFA and its metabolites: acetoacetic acid (AcAc), beta hydroxybutyric acid (BOH), and triglyceride (TG) were assessed in five normal male subjects. The threshold of response was determined by administering intravenous glucagon in a graded dose-response fashion, andassessing the magnitude of change in FFA and its metabolites. A prompt rise in FFA concentration occurred after glucagon injection, and was associated with a synchronous elevation in both AcAc and BOH concentration in plasma. The rise in FFA concentration was maximal with the glucagon dosage of 0.5 mug./kg. with no greater FFA response seen athigher hormone dosage. In contrast, the rise in plasma ketones was linearly related to thedosage of glucagon but not to the corresponding rise in FFA concentration. The behavior of plasma triglyceride concentration following glucagon challenge also contrasted with the linear rise in ketone concentration. At the lowest dosage of glucagon, TG concentration rose transiently, while at the highest two dosages the concentration of TG was reduced. The transitional dosage of hormone at which no change in TG concentration was observed was approximately 0.5 mug./kg. Comparing our in vivo data with the conclusions reached from published liver perfusion studies, it can be suggested that in the dosages employed, glucagon acutely elevates plasma FFA concentration and modulates their metabolism by augmenting conversion to AcAc and BOH while tending to reduce conversion to TG in man.