Glucagon suppression improves glucoregulation in moderate but not chronic severe diabetes

To determine the effectiveness of glucagon suppression in improving glucose homeostasis in diabetes, tracer-determined glucose kinetics were measured during a 6-h somatostatin infusion in six alloxan-diabetic dogs (moderately severe diabetes) and five depancreatized dogs deprived of insulin treatment for 3 days (prolonged severe diabetes). Plasma immunoreactive glucagon (IRG) decreased 70 +/- 9% in the alloxan-diabetic and 80 +/- 4% in the depancreatized dogs. Portal vein levels of plasma immunoreactive insulin (IRI) fell (17.0 +/- 2.3 to 4 micro.5 +/- 0.4 microU/ml) as did peripheral vein IRI levels (6.7 +/- 0.9 to 4.7 +/- 0.5 microU/ml) in the alloxan-diabetic dogs. In the depancreatized dogs plasma IRI levels were undetectable. Plasma glucose concentrations fell (278 +/- 17 to 169 +/- 12 mg/dl) during IRG suppression in the alloxan-diabetic dogs due to a rapid and sustained decrease in glucose production (Ra) (6.0 + 0.9 to 3.6 + 0.3 mg X kg-1 X min-1). Glucose disappearance (Rd) decreased gradually (5.9 + 0.6 to 3.9 + 0.2 mg X kg-1 X min-1). In contrast, in the depancreatized dogs, IRG suppression did not alter glucose concentrations or kinetics. Thus, glucagon suppression decreased glycemia by decreasing Ra only in moderately severe diabetes. However, this was associated with decreased rather than improved glucose utilization. The ineffectiveness of glucagon suppression during prolonged severe diabetes could relate to the degree and duration of the metabolic derangement and/or indicate that the continuous presence of some insulin is necessary for glucagon suppression to improve glucose homeostasis.