Prevention of overt hypoglycemia during exercise: Stimulation of endogenous glucose production independent of hepatic catecholamine action and changes in pancreatic hormone concentration

These studies were conducted to determine the magnitude and mechanism of compensation for impaired glucagon and insulin responses to exercise. For this purpose, dogs underwent surgery >16 days before experiments, at which time flow probes were implanted and silastic catheters were inserted. During experiments, glucagon and insulin were fixed at basal levels during rest and exercise using a pancreatic clamp with glucose clamped (PC/GC; n = 5), a pancreatic clamp with glucose unclamped (PC; n = 7), or a pancreatic clamp with glucose unclamped + intraportal propranolol and phentolamine hepatic α-and β-adrenergic receptor blockade (PC/HAB; n = 6). Glucose production (R_a) was measured isotopically. Plasma glucose was constant in PC/GC, but fell from basal to exercise in PC and PC/HAB. R_a was unchanged with exercise in PC/GC, but was slightly increased during exercise in PC and PC/HAB. Despite minimal increases in epinephrine in PC/GC, epinephrine increased approximately sixfold in PC and PC/HAB during exercise. In summary, during moderate exercise, 1) the increase in R_a is absent in PC/GC; 2) only a moderate fall in arterial glucose occurs in PC, due to a compensatory increase in R_a; and 3) the increase in R_a is preserved in PC/HAB. In conclusion, stimulation of R_a by a mechanism independent of pancreatic hormones and hepatic adrenergic stimulation is a primary defense against overt hypoglycemia.