J. Movassat et B. Portha, Beta-cell growth in the neonatal Goto-Kakisaki rat and regeneration after treatment with streptozotocin at birth, DIABETOLOG, 42(9), 1999, pp. 1098-1106
Aims/hypothesis. In the Goto-Kakisaki rat, a genetic model of non-insulin d
ependent diabetes, we have recently reported that as early as fetal age, th
ere 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 therefo
re important to investigate the beta-cell growth potential in young Goto-Ka
kisaki rats.
Methods. 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 a
poptosis; 3. the effectiveness of beta-cell regeneration after damage cause
d by neonatal treatment with streptozotocin.
Results. The replication rate in vivo of beta cells and the beta-cell apopt
osis 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-Ka
kisaki groups. Treatment with streptozotocin reduced the total beta-cell ma
ss to the same extent in both Wistar and Goto-Kakisaki rats on day 4 compar
ed with the corresponding normal values in Wistar and Goto-Kakisaki neonate
s. From day 4 to day 7, spontaneous beta-cell regeneration was manifest in
both groups. Compared with the Wistar streptozotocin group, the net value o
f the beta-cell mass added during this period was more limited in the Goto-
Kakisaki streptozotocin group, despite the replication activity of the resi
dual beta cells being increased in this group to the same extent as in the
Wistar streptozotocin group.
Conclusion/interpretation. We therefore suggest: 1. that the reduced beta-c
ell mass in the untreated neonatal Goto-Kakisaki rat does not appear to ref
lect 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 afte
r streptozotocin insult in the neonatal Goto-Kakisaki rat, although to a le
sser extent compared with that in streptozotocin-treated Wistar neonates.