Effects of Growth Hormone and Insulin-Like Growth Factor I on Endocrine Function of Human Fetal Islet-Like Cell Clusters During Long-Term Tissue Culture

The effects of recombinant human growth hormone (GH, 1 µg/ml) and insulin-like growth factor I (IGF-I, 200 ng/ml) on the production of insulin and glucagon by human fetal islet-like cell clusters (ICCs) were studied in tissue culture. ICCs were derived after collagenase digestion and culture of pancreases from 16 fetuses (mean gestational age 15.6 wk). The ICCs were cultured with or without GH or IGF-I for 7 or 31 days. Basal rates of insulin and glucagon production were not altered by GH during the first 17 days of culture, but the release of both hormones was increasingly augmented by GH during the last 2 wk of culture (131% increase in insulin and 85% in glucagon compared with controls). ICCs cultured for 7 days in the presence of GH secreted more insulin when incubated for 120 min in 20 mM than in 2 mM glucose (2.1-fold response, P < .05), whereas ICCs mantained in basal medium did not respond to glucose. GH had no effect on DNA and insulin content or insulin biosynthesis. Exogenous IGF-I caused a 28% suppression of insulin release (P < .05) between days 4 and 10 of culture but induced a 49% increase in the mean secretion rate during the last week (days 25–31, P < .01). Glucagon release was not affected by exogenous IGF-I. In contrast to GH, exogenous IGF-I induced a twofold increase in the DNA content of the 7-day-cultured ICCs. However, insulin biosynthesis and release were markedly suppressed. We conclude that GH influences the functional maturation of human fetal islet cells in vitro. The effects of GH could not be reproduced by the addition of IGF-I, suggesting a direct rather than a somatomedin-mediated action for GH.