Actions of growth hormone: Enhancement of insulin utilization with inhibition of insulin effect on blood glucose in dogs

Abstract

The disappearance of labeled immunoreactive insulin (L-IRI) from blood serum was measured in dogs, after a trace dose of 131I-insulin, given intravenously, had intermixed in the body fluids. The degree of labeling of insulin was low, and the same preparation was used in all tests. The disappearance of L-IRI followed an exponential course, the mean value of the fractional rate constant ( k) was 1.86 ± 0.20 per cent min. −1. An integral method of analysis of the data gave similar values. Growth hormone (GH, 2 mg./Kg. of body weight/day) injected for 4 days, did not alter this fractional rate appreciably. However, the mass rate of irreversible loss of insulin was greatly increased (19-fold), due chiefly to elevation of endogenous immunoreactive insulin in “postabsorptive” serum. The enhanced rate of utilization of insulin, induced by GH, was thus dependent on, and coupled with increased secretion of insulin. During GH administration, serum glucose rose, but to a lesser degree than insulin: the IRI/glucose ratio (23 microunits/mg. under the control conditions) rose, about 10-fold. Serum free fatty acid, and esterified fatty acid levels were both increased by GH. The responsiveness to insulin, within 2 hours of intravenous injection of 0.1 unit/Kg., was tested in these dogs. During GH treatment, the reduction in serum glucose was less rapid, but the sharp fall in free fatty acids was not prevented. Insulin did not affect esterified fatty acid levels, under both the control and GH treatment conditions, however. A hypothesis is outlined for the effect of GH in diverting preferentially the utilization of the large amounts of insulin from processes of carbohydrate metabolism to those involved in protein synthesis.