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PERSISTENT EFFECT OF SUSTAINED HYPERGLUCAGONEMIA ON GLUCOSE PRODUCTION IN MAN

Diabetes and Metabolism Research Laboratory; Endocrine Research Unit; Departments of Medicine and Physiology; Mayo Clinic and Mayo Medical School Rochester, MN

In man prolonged infusions of glucagon cause a transient increase in glucose production. To determine whether this represents complete loss of effect of hyperglucagonemia on the liver or merely decreased hepatic responsiveness, glucagon (3 ng/kg/min) was infused in six normal subjects to produce sustained hyperglucagonemia for 180 min; at this time glucagon infusions were stopped for 60 min, then restarted at the same rate for 60 min and finally increased to 7.5 ng/kg/min for 30 min. Glucose production (Ra) and utilization (Rd) were measured isotopically. Initially glucagon infusion increased Ra transiently from 1.8±0.1 mg/kg/min to a maximum at 15 min of 2.5±0.2 mg/ kg/min (p<.01); Ra returned to basal values by 60 min and remained there until the glucagon infusion was stopped, whereupon it abruptly declined to a nadir of 1.4±0.1 mg/kg/min, a value significantly below baseline levels, p<.005. Upon restarting the glucagon infusion, Ra increased to a similar extent as observed with the initial infusion and then returned to basal levels; when the glucagon infusion rate was increased to 7.5 ng/kg/min, Ra again increased. These results indicate that sustained hyperglucagonemia, despite apparent waning of its effect, continues to modulate hepatic glucose production.

Received August 15, 1978.

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