IMPORTANCE OF GLUCAGON IN MEDIATING EPINEPHRINE-INDUCED HYPERGLYCEMIA IN ALLOXAN-DIABETIC DOGS

In normal dogs epinephrine stimulates glucose production (Ra) independently of glucagon. To investigate the role of this interaction in diabetes, epinephrine (0.1 .mu.g .cntdot. kg-1 .cntdot. min-1) was infused for 90 min in 5 alloxan-diabetic dogs in the presence or absence of somatostatin (0.1 .mu.g .cntdot. kg-1 .cntdot. min-1). In response to epinephrine, glycemia rose by 40% reflecting a near maximal (122%) increase in Ra. Plasma glucagon (IRG) rose to 953 pg/ml; insulin (IRI) increased minimally. When somatostatin was infused with epinephrine to prevent the rise of IRG and IRI, there was only a marginal increase of glucose concentration (12%) and production (38%). The effect of somatostatin was reversed by infusing glucagon (10 ng .cntdot. kg-1 .cntdot. min-1) together with epinephrine and somatostatin into 5 additional alloxan-diabetic dogs. Increments in IRG, glycemia and Ra were fully reestablished. A 100% free fatty acid increase was observed in all 3 groups, indicating that the lipolytic effect of epinephrine was independent of glucagon. In diabetic dogs, in contrast to normal dogs epinephrine induced a marked and prolonged increase in glucose concentration and production mostly through a stimulation of IRG secretion.