Carbohydrate Tolerance and Insulin Receptor Binding in Children with Hypopituitarism: Responses after Acute and Chronic Human Growth Hormone Administration*

We investigated carbohydrate tolerance in response to a standard oral glucose tolerance test (OGTT) and an iv insulin tolerance test (IVITT) in a group of GH-deficient children before and after short term (acute) and prolonged (chronic) human GH (hGH) administration. Erythrocyte and monocyte insulin receptor binding were assessed during each treatment phase. In the untreated state, OGTT responses demonstrated basal hypoinsulinemia and diminished insulin secretion compared to controls. Glucose responses, however, were only slightly greater than the controls. IVITT suggested enhanced insulin sensitivity. However, we were unable to demonstrate significant differences in either erythrocyte or monocyte insulin receptor binding to account for these findings. After chronic hGH administration, insulin secretion increased following oral glucose ingestion, but glucose tolerance was impaired, while the sensitivity to exogenous insulin was unchanged. Alterations in insulin binding did not appear to be associated with these changes. After acute hGH administration (three im injections in a 12-h period), the IVITT showed marked impairment associated with a diminution in erythrocyte insulin receptors. Plasma insulin concentrations were not increased, but a significant rise in plasma FFA was observed. These data suggest that demonstrable alterations in insulin binding may account for a component of the insulin resistance associated with acute hGH administration, but that alterations in carbohydrate homeostasis between states of GH deficiency and chronic hGH treatment remain largely a function of intracellular metabolism modulated at sites distal to the insulin receptor.