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


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 apoptosis; 3. the effectiveness of beta-cell regeneration after damage caused by neonatal treatment with streptozotocin.


RESULTS
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.


CONCLUSIONS
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.
Movassat
J
J
Laboratory Physiopathology of Nutrition, University Paris/D. Diderot, CNRS ESA 7059, Paris, France.
Portha
B
B
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D002455:Cell Division; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010179:Pancreas / Q000254:growth & development*; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D012038:Regeneration / Q000187:drug effects; D013045:Species Specificity; D013311:Streptozocin / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin