Growth hormone regulation of DNA replication, but not insulin production, is partly mediated by somatomedin-C/insulin-like growth factor I in isolated pancreatic islets from adult rats

Abstract

We have investigated whether the previously demonstrated stimulatory actions of growth hormone on DNA synthesis and (pro)insulin biosynthesis and release of isolated adult rat islets of Langerhans are mediated by an autocrine release of somatomedin-C/insulin-like growth factor I (SM-C/IGF I). In medium containing 1% fetal calf serum, the presence of 16.7 mmol/l glucose, or 2.7 mmol/l glucose supplemented with a concentrate of essential amino acids, caused a significant increase in 3H-thymidine incorporation and insulin release compared to 2.7 mmol/l glucose alone but no increase in SM-C/IGF I release. Further supplementation with 1 microgram/ml growth hormone increased 3H-thymidine incorporation and SM-C/IGF I release within all groups, and insulin release in the 16.7 mmol/l glucose and 2.7 mmol/l plus amino acid groups. The ability of growth hormone to increase 3H-thymidine incorporation in the presence of 16.7 mmol/l glucose, but not its action on insulin release, was partly inhibited by a monoclonal antibody against SM-C/IGF I (control cultures 100%; growth hormone alone 261 +/- 27%, mean +/- SEM; growth hormone + anti-SM-C/IGF I 179 +/- 21%; p less than 0.05, n = 18). Growth hormone, but not 100 ng/ml SM-C/IGF I, increased insulin biosynthesis assessed as immunoprecipitable 3H-labelled insulin by 45%, but this was accompanied by a similar increase in overall protein synthesis. Similarly growth hormone, but not SM-C/IGF I caused a 75% increase in glucose oxidation by islets. Both growth hormone and SM-C/IGF I failed to increase the cellular uptake of alpha-aminoisobutyric acid or 3-O-methyl glucose over a 90 min period.(ABSTRACT TRUNCATED AT 250 WORDS)