ISSN:
1432-0428
Keywords:
Total glucose appearance
;
glucose production
;
glucose disappearance
;
metabolic clearance of glucose
;
tracer-determined glucose turnover
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00274224
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