DNA replication in transplanted and endogenous pancreatic islets of obese-hyperglycemic mice at different stages of the syndrome.

It was the aim of the present study to examine, at different stages of the obese-hyperglycemic syndrome, rates of islet-cell DNA replication in endogenous pancreatic and grafted islets of such mice. For this purpose obese-hyperglycemic mice were given an islet transplant prepared from lean mice under the kidney capsule. Two weeks later the animals were given an IP injection of 3H-thymidine one hour before being killed. Autoradiography of pancreas and kidney sections indicated the highest labeling index (LI) for the endogenous islet cells in the youngest obese mice (6 weeks old), which was more than fivefold higher than that of lean, normoglycemic controls. The LI, however, decreased extensively with age. The transplanted islets had LI, which were higher and constant during the most intense period of the syndrome, but again there was a decrease in the oldest mice. By isolating and transplanting islets of the oldest obese mice (greater than 12 months) into younger obese mice, it was possible to revive the high cell replicatory activity of the ob/ob islets. Starvation for three days was found to markedly decrease the rate of islet cell DNA replication. Adrenalectomy of obese-hyperglycemic mice resulted in a decrease of the serum glucose and insulin concentrations; concomitantly, there was a decrease of LI of both transplanted and endogenous islets. Thus, it seems as if the attenuation of the hyperglycemia is most probably responsible for the decline of the islet cell replication with increasing age in obese-hyperglycemic mice.