REGULATION OF FREE FATTY-ACID METABOLISM BY GLUCAGON

Glucagon may regulate FFA metabolism in vivo. To test this hypothesis, six healthy male volunteers were infused with somatostatin, to inhibi t endogenous hormone secretion, and insulin, glucagon, and GH to repla ce endogenous secretion of these hormones. In the hypoglucagonemia exp eriments, the glucagon infusion was omitted, and in the hyperglucagone mic experiments glucagon was infused at 1.3 ng/kg.min, to produce phys iological hyperglucagonemia. In two sets of control experiments, gluca gon was infused at 0.65 ng/kg.min, in order to maintain peripheral eug lucagonemia, and the plasma glucose concentrations were clamped at the levels observed in either the hypo- or hyperglucagonemic experiments. Rates of FFA and glycerol (an index of lipolysis) appearance (Ra) wer e estimated with the isotope dilution method using [1-C-14]palmitate a nd [H-2(5)] glycerol. Plasma glucagon concentrations decreased during the hypoglucagonemic experiments (85 +/- 12 vs. 123 +/- 22 ng/L, P < 0 .05) and increased during the hyperglucagonemic experiments (186 +/- 2 0 vs. 125 +/- 15 ng/L, P < 0.05), whereas other hormone concentrations remained the same. Hypoglucagonemia resulted in equivalent suppressio n of FFA Ra (3.7 +/- 0.2 vs. 5.9 vs. 0.3 mumol/kg.min, P < 0.01) and g lycerol Ra (1.2 +/- 0.2 vs. 2.2 +/- 0.5 mumol/kg.min, P < 0.05). Simil arly, hyperglucagonemia resulted in equivalent stimulation of FFA Ra ( 5.2 +/- 0.4 vs. 3.7 +/- 0.3 mumol/kg.min, P < 0.05) and glycerol Ra (1 .5 +/- 0.3 vs. 1.1 +/- 0.1 mumol/kg.min, P < 0.05). These results indi cate that glucagon has a physiological role in the regulation of FFA m etabolism in vivo.