Effects of platelet-derived growth factor and somatomedin-C/insulin-like growth factor I on the deoxyribonucleic acid replication of fetal rat islets of Langerhans in tissue culture

Abstract

The effects of platelet-derived growth factor (PDGF) on DNA replication and release of insulin and somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) from cultured fetal rat islets have been studied. In medium containing 1% fetal calf serum and 16.7 mM glucose, both PDGF (2-10 ng/ml) and SM-C/IGF-I (100 ng/ml) stimulated DNA replication 2-fold. The growth stimulatory effects of the two peptides were additive. In the absence of serum, SM-C/IGF-I, but not PDGF, stimulated DNA replication. Under conditions of PDGF-stimulated DNA replication there was no increased release of either insulin or SM-C/IGF-I into the culture medium. An antibody against SM-C/IGF-I which inhibited SM-C/IGF-I-stimulated DNA replication did not affect PDGF-stimulated DNA replication. Similarly, an antibody against PDGF did not affect DNA replication stimulated by SM-C/IGF-I. It is concluded that PDGF stimulates islet cell DNA replication. This is the first demonstration of a tissue of nonmesodermal origin responding to PDGF. Stimulation of DNA replication appears to be independent of SM-C/IGF-I release, and furthermore, the results indicate that the islets do not produce PDGF-like substances themselves. It is suggested that PDGF is of importance for fetal islet development.