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PERSISTENT STIMULATORY EFFECT OF GLUCAGON ON GLUCOSE PRODUCTION DESPITE DOWNREGULATION

Departments of Medicine and Physiology, Vanderbilt University School of Medicine Nashville, Tennessee 37232

Presented in part at the meetings of the American Society for Clinical Investigation, San Francisco, May, 1978.

The rise and subsequent return to basal of glucose production (Ra) during a constant glucagon infusion ("downregulation") has suggested to some workers that glucagon's effects are evanescent. To examine whether glucagon displays persistent biological activity even after downregulation, 6 healthy males received an 8 hour infusion of somatostatin and glucagon, with 3H-3-glucose to measure glucose turnover. Ra rose from 2.8 ± 0.3 to 4.2 ± 0.3 mg/kg·min at 90 minutes, returned to basal levels at 150 minutes, and remained at this level for the ensuing 330 minutes. Six additional subjects received an 8 hour somatostatin infusion, with glucagon administered concomitantly for the first 5 hours. Glucagon withdrawal at 5 hours produced an immediate decline in Ra from 1.8 ± 0.2 to 0.9 ± 0.2 mg/kg·min. Thus, even after downregulation the maintenance of basal Ra is dependent on circulating glucagon.

Accepted July 1, 1978.