Growth hormone has classically been considered to be a diabetogenic hormone. However, in insulin-dependent diabetic man the mechanism of its ketogenic activity has not been resolved. Therefore, this study was designed to examine three aspects of growth hormone's ketogenic activity: first, whether growth hormone's ketogenic activity can be entirely accounted for by its lipolytic effect; second, whether growth hormone's ketogenic activity is rapid or delayed in onset; and third, whether growth hormone may exert ketogenic activity indirectly by altering the plasma concentration of other ketone body-regulatory hormones (i.e. insulin, glucagon, and cortisol). In order to obtain data relative to these three questions, growth hormone was administered to six insulin dependent, ketosis-prone diabetic subjects. Both acute and prolonged growth hormone exposure studies were performed in all subjects and compared with a control study. Plasma free-fatty-acid concentration was elevated in all studies by heparin administration to assess growth hormone's ketogenic activity independent of its lipolytic effect.
Our results suggest that, in insulin-dependent diabetic man, growth hormone exerts profound ketogenic activity that is delayed at least 60 minutes. Although this ketogenic activity may be a direct effect of the hormone, our results indicate that at least two indirect mechanisms may participate in raising plasma ketone body concentration. First, growth hormone may exert ketogenic activity indirectly by elevating plasma free-fatty-acid substrate concentration. Second, growth hormone administration results in a significant reduction in circulating plasma free–insulin concentration, an observation that has not been previously reported. Since the diabetics in this study were given a fixed dose of exogenous insulin, these results suggest that growth hormone alters either the absorption and/or degradation of injected insulin in diabetic man. This latter mechanism may account for our observation that growth hormone exerts ketogenic activity independent of its lipolytic effect.
