Summary
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 μg·kg−1· min−1), (2) somatostatin with insulin replacement (100 μU·kg−1min−1) or (3) glucagon (6 ng·kg−1· min−1) together with somatostatin and transient insulin replacement. When somatostatin was given alone, plasma glucagon (p<0.004) and insulin (p<0.0001) were suppressed. Glucose production and disappearance and plasma glucose concentrations fell (p<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 goups 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 μmol·kg·−1min−1 (p<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±1.7μmol·kg−1·min.−1 (p<0.02). When glucagon was infused together with somatostatin and insulin replacement, plasma glucagon (p<0.0002) increased and plasma glucose levels rose (p<0.001) due to a transient increase in glucose production. Metabolic clearance of glucose did not change significantly. There was a marked increase in futile cycling from 12.2±1.7 to 21.7±1.7μmol· kg−1·min−1 (p<0.0001) in response to exogenous glucagon excess. There was a slight (p<0.01) drop in free fatty acid levels with somatostatin. Free fatty acid levels nearly doubled (p<0.025) with the infusion of glucagon together with somatostatin. In conclusion, (a) futile cycling was increased in alloxan-diabetic dogs; (b) glucagon suppression can suppress futile cycling only if total insulin deficiency is prevented; and (3) hyperglucagonaemia increases futile cycling, and this effect is more pronounced during insulin deficiency.
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Lickley, H.L.A., Kemmer, F.W., El-Tayeb, K.M.A. et al. Importance of glucagon in the control of futile cycling as studied in alloxan-diabetic dogs. Diabetologia 30, 175–182 (1987). https://doi.org/10.1007/BF00274224
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DOI: https://doi.org/10.1007/BF00274224