We have investigated the effects on carbohydrate metabolism of human GH produced by recombinant DNA technology (methionyl-hGH) compared with pituitary hGH, Twelve normal adult male subjects received four daily im injections of either methionyl-hGH or pituitary hGH in a double blind, crossover study. Oral glucose tolerance tests and assays of insulin binding to peripheral monocytes were performed before the initial administration and 12 h after the fourth injection of both hGH preparations. Both methionyl-hGH and pituitary hGH resulted in significant carbohydrate intolerance, with a rise in fasting plasma glucose from 96.6 ± 2.9 to 105.9 ± 3.0 mg/ml (mean ± SEM) after pituitary hGH and from 96.2 ± 1.5 to 107.5 ± 3.3 mg/dl after methionyl-hGH (P < 0.01). The area under the glucose tolerance curve increased by 34% after pituitary hGH and by 37% after methionyl-hGH. With both hGH preparations, carbohydrate intolerance was associated with marked hyperinsulinemia, with a rise in fasting plasma insulin levels from 9.4 ± 1.2 to 33.2 ± 7.8 μU/ml after pituitary hGH and from 7.4 ± 1.1 to 45.8 ± 11.1 μU/ml after methionyl-hGH (P < 0.01). The integrated plasma insulin levels during the oral glucose tolerance test tripled after both hGH preparations. The pronounced insulin resistance could not be attributed to an alteration in insulin receptor concentrations. Both hGH preparations were associated with small reductions in insulin binding o t monocytes at tracer concentrations, but the decline in binding was not statistically significant. The calculated binding sites per cell and Kē were not significantly altered by hGH administration. We conclude that methionyl-hGH and pituitary hGH are indistinguishable in their ability to induce insulin-resistant carbohydrate intolerance. This decrease in insulin sensitivity cannot be attributed to an alteration in insulin binding, and presumably represents a postreceptor defect in insulin action.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical