Islet cell thymidine kinase activity as indicator of islet cell proliferation in rat pancreas

Abstract

The activity of thymidine kinase (TK;EC 2.7.1.21) in homogenates of isolated rat islets of Langerhans was measured and correlated with the DNA replicatory activity of the islet cells. Adult and fetal rat islets were cultured in medium with 2.7 or 16.7 mM glucose or 16.7 mM glucose and 1 microgram/ml human growth hormone. In both types of islets, 16.7 mM glucose doubled [3H]thymidine incorporation compared with 2.7 mM glucose, and the addition of growth hormone caused a further increase in DNA replication. TK activity in the islets showed similar changes in response to glucose and growth hormone. The correlation between [3H]thymidine incorporation and TK activity was thus highly significant. Cell-cycle analysis of cultured fetal rat islets showed that TK activity was preferentially expressed during the S phase of the cell cycle. TK activity of freshly isolated islets declined with the age of the animal. In pancreatic sections, the islet cell autoradiographic labeling index after [3H]thymidine administration in vivo likewise declined with age and was correlated with the TK activity in freshly isolated islets. It is suggested that measurements of islet TK activity can be used as index of islet cell proliferation; this method has the distinct advantage of avoiding the cumbersome procedure of preparing and scoring autoradiograms.