Importance of glucagon in the control of futile cycling as studied in alloxan-diabetic dogs.

In order to determine the role of glucagon in futile or substrate cycling in diabetes, we measured tracer determined glucose kinetics during a combined infusion of 2-3H-glucose (total glucose production) and 6-3H-glucose (glucose production) in six alloxan-diabetic dogs. The animals received either a 420 min infusion of (1) somatostatin alone (0.3 microgram X kg-1 X min-1), (2) somatostatin with insulin replacement (100 microU X kg-1 X min-1) or (3) glucagon (6 ng X kg-1 X min-1) together with somatostatin and transient insulin replacement. When somatostatin was given alone, plasma glucagon (p less than 0.004) and insulin (p less than 0.0001) were suppressed. Glucose production and disappearance and plasma glucose concentrations fell (p less than 0.0001), but the metabolic clearance of glucose did not change significantly. In the basal state, futile cycling comprised 29 +/- 4%, 33 +/- 4% and 33 +/- 3% of total glucose production in the three groups of studies, which is high compared to normal dogs. The absolute rate of futile cycling fell slightly but significantly from 10.0 +/- 1.7 to 8.3 +/- 1.7 mumol X kg X -1 min-1 (p less than 0.0008). When insulin replacement was given during somatostatin infusion to correct for the small somatostatin-induced insulin suppression, there were similar changes in plasma glucagon, glucose concentrations and glucose kinetics as seen during the infusion of somatostatin alone. Futile cycling decreased to a slightly greater extent from 12.8 +/- 2.8 to 9.5 +/- 1.7 mumol X kg-1 X min.-1 (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)