KINETICS OF GLUCAGON IN MAN - EFFECTS OF STARVATION

The kinetics of glucagon in man was evaluated by continuously infusing crystalline glucagon in normal postabsorptive subjects at rates of 1.5, 3.0 and 6.0 ng/kg per min, and in obese subjects at a rate of 120 ng/m2 per min. The obese group was studied in the postabsorptive state and after 3 days and 3-4 wk of starvation. In the postabsorptive state the increment in plasma glucagon was directly proportional to the infusion rate, indicating that glucagon turnover is linear over the range of plasma concentrations studied (200-600 pg/ml). The metabolic clearance rate of glucagon (MCRG) was 537 .+-. 27 (SE) ml/m2 per min, which is comparable to that reported for insulin. The basal systemic delivery rate (BSDRG) was 51 .+-. 5 (SE) ng/m2 per min, which extrapolates to a 24-h glucagon delivery rate of 139 .+-. 14 (SE) .mu.g/day. MCRG and BSDRG in the postabsorptive state were comparable in obese and nonobese subjects. Hyperglucagonemia induced by a 3-day fast was associated with a 20% reduction in MCRG, but no change in BSDRG. After 3-4 wk of fasting, MCRG declined further to 35% below baseline. Plasma glucagon fell, returning to postabsorptive levels, as BSDRG decreased 37% below postabsorptive values. In postabsorptive man glucagon removal is proportional to the plasma concentration. During early starvation hyperglucagonemia results primarily from decreased glucagon removal rather than hypersecretion. In prolonged fasting plasma glucagon returns to baseline levels as a consequence of a reduction in secretion in association with a progressive decline in metabolic clearance.