Summary
The response to exogenous glucagon administration was examined in 5 moderately obese subjects (180±20% ideal body weight) and 5 normal weight controls. Changes in the plasma concentration of glucagon, insulin, glucose, free fatty acids, and β-hydroxybutyrate were observed after both a 1.0 µg/kg or 2.0 µg/kg bolus i.v. glucagon injection. At the lowest dose of glucagon (1.0 µg/kg) the obese group exhibited a markedly altered tissue response. In contrast to the uniform increase in free fatty acid and β-hydroxybutyrate concentration in all normal weight subjects, 4 of the 5 and 3 of the 5 obese subjects respectively demonstrated a decline in the plasma concentration of these two hormonally sensitive substrates. This ‘resistance’ to the catabolic action of glucagon was overcome at a higher dosage of glucagon (2.0 µg/kg) and was accompanied by a simultaneous increase in the ratio of glucagon administered to the insulin secreted. Our study demonstrates a relative resistance to two of the catabolic actions of glucagon in obesity. Although the mechanism of this resistance is not resolved by this study, the hyperinsulinism present in all our obese subjects may be a contributory factor.
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This investigation was supported by grants from the KROC Foundation, The American Diabetes Association, and the Eli Lilly Company.
This work was done during tenure of D. S. Schade as an American Diabetes Research Associate.
Lovelace-Bataan Clinic.
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Schade, D.S., Eaton, P.R., Pommer, I. et al. Modulation of the catabolic activity of glucagon by endogenous insulin secretion in obese man. Acta diabet. lat 14, 62–72 (1977). https://doi.org/10.1007/BF02624664
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DOI: https://doi.org/10.1007/BF02624664