Beta-cell growth in the neonatal Goto-Kakisaki rat and regeneration after treatment with streptozotocin at birth

Abstract

In the Goto-Kakisaki rat, a genetic model of non-insulin dependent diabetes, we have recently reported that as early as fetal age, there is a restriction of the beta-cell mass which is maintained in the adult animal and is detectable before the onset of hyperglycaemia. It is therefore important to investigate the beta-cell growth potential in young Goto-Kakisaki rats. We have studied in 4 and 7-day-old Goto-Kakisaki neonates: 1. the in vivo replication rate of the beta cell; 2. the occurrence of beta-cell apoptosis; 3. the effectiveness of beta-cell regeneration after damage caused by neonatal treatment with streptozotocin. The replication rate in vivo of beta cells and the beta-cell apoptosis were similar in untreated Wistar and Goto-Kakisaki neonates on days 4 and 7 whereas the total beta-cell masses were reduced to 50 % in the Goto-Kakisaki groups. Treatment with streptozotocin reduced the total beta-cell mass to the same extent in both Wistar and Goto-Kakisaki rats on day 4 compared with the corresponding normal values in Wistar and Goto-Kakisaki neonates. From day 4 to day 7, spontaneous beta-cell regeneration was manifest in both groups. Compared with the Wistar streptozotocin group, the net value of the beta-cell mass added during this period was more limited in the Goto-Kakisaki streptozotocin group, despite the replication activity of the residual beta cells being increased in this group to the same extent as in the Wistar streptozotocin group. We therefore suggest: 1. that the reduced beta-cell mass in the untreated neonatal Goto-Kakisaki rat does not appear to reflect a reduction in the rate of beta-cell replication or an increased beta-cell death by apoptosis but is potentially due to an impaired rate of beta-cell neogenesis, and 2. that beta-cell regeneration can be reactivated after streptozotocin insult in the neonatal Goto-Kakisaki rat, although to a lesser extent compared with that in streptozotocin-treated Wistar neonates.