THE EFFECT OF ACUTE GLUCAGON REMOVAL ON THE METABOLIC RESPONSE TO STRESS HORMONE INFUSION IN THE CONSCIOUS DOG

The effect of acute glucagon removal on glucose metabolism following l ong-term (70-hour) stress hormone infusion (day 3) was investigated in 20-hour-fasted conscious dogs. Stress hormone infusion increased arte rial plasma glucagon, cortisol, epinephrine, and norepinephrine (simil ar to fivefold), as well as arterial plasma glucose (Delta 82 +/- 16 m g/dL) and insulin (Delta 26 +/- 5 mu U/mL). After assessing basal gluc ose metabolism on day 3, the long-term glucagon infusion was discontin ued (n = 6), and the remaining hormones were infused for an additional 180 minutes. Constant glycemia was maintained by an exogenous glucose infusion. In five dogs, the stress hormone infusion containing glucag on was continued for 180 minutes. Glucose production and gluconeogenes is were assessed using tracer and arteriovenous-difference techniques. Acute removal of glucagon decreased arterial plasma glucagon from 220 +/- 24 to 32 +/- 4 pg/mL and net hepatic glucose output (Delta 1.6 +/ - 0.3 mg/kg/min). Net hepatic handling of lactate, alanine, and glycer ol was not altered. The efficiency of gluconeogenesis, on the other ha nd, was decreased by 40%. Liver biopsies taken following discontinuati on of glucagon indicated that both H-3- and C-14-glucose accumulated i n glycogen. The calculated rate of plasma glucose and gluconeogenic pr ecursor diversion to glycogen increased by fivefold and fourfold, resp ectively. The increased gluconeogenic precursor diversion to glycogen accounted for 58% of the decrease in the efficiency of gluconeogenesis . in conclusion, acute removal of glucagon during stress hormone infus ion decreased net hepatic glycogenolysis in the face of prevailing hyp erglycemia and hyperinsulinemia, while having minimal effects on the g luconeogenic process per se. Copyright (C) 1994 by W.B. Saunders Compa ny