Glucose-stimulated DNA replication of the pancreatic islets during the development of the rat fetus. Effects of nutrients, growth hormone, and triiodothyronine.

Abstract

DNA replication and insulin release have been studied in islets isolated, using a tissue culture technique, from rat fetuses of different gestational ages. The islets were cultured for 3 days in media with high and low concentrations of glucose or amino acids. The DNA replication was determined by autoradiography and the insulin secreted into the medium was measured by radioimmunoassay. In islets of 22-day-old fetuses, DNA replication was stimulated by both glucose and amino acids. At gestational days 18 and 20, only amino acids increased DNA replication. However, both high glucose and high amino acid concentrations increased the islet insulin secretion into the culture medium at all ages studied. In an attempt to induce glucose-sensitive DNA replication in vitro, islets obtained from 18- and 20-day-old fetal pancreata were cultured in the presence of either triiodothyronine or human growth hormone. Triiodothyronine failed to influence either DNA replication or insulin release. Growth hormone, however, increased DNA replication and insulin release in both the experimental groups but did not induce a growth response to glucose. It is concluded that the appearance of glucose-stimulated B-cell growth is a late event in the fetal development of the rat, parallelling the late maturation of both insulin biosynthesis and release. This finding may explain the difficulties in producing islet cell hyperplasia and diabetic fetopathy previously shown in rat models of diabetes in pregnancy.