Besides the fetal period, the suckling period is a critical time window in determining long-term metabolic health. We undertook the present study to elucidate the impact of a diabetic suckling environment alone or associated with an in utero diabetic environment on beta cell mass development and the risk of diabetes in the offspring in the long term. To that end, we have compared two experimental settings. In setting 1, we used Wistar (W) rat newborns resulting from W ovocytes (oW) transferred into diabetic GK rat mothers (pGK). These oW/pGK neonates were then suckled by diabetic GK foster mothers (oW/pGK/sGK model) and compared to oW/pW neonates suckled by normal W foster mothers (oW/pW/sW model). In setting 2, normal W rat newborns were suckled by diabetic GK rat foster mothers (nW/sGK model) or normal W foster mothers (nW/sW model). Our data revealed that the extent of metabolic disorders in term of glucose intolerance and beta cell mass are similar between rats which have been exposed to maternal diabetes both pre- and postnatally (oW/pGK/sGK model) and those which have been exposed only during postnatal life (nW/sW model). In other words, being nurtured by diabetic GK mothers from birth to weaning was sufficient to significantly alter the beta cell mass, glucose-induced insulin secretion and glucose homeostasis of offspring. No synergistic deleterious effects of pre-and postnatal exposure was observed in our setting.
Nupr1 deletion protects against glucose intolerance by increasing beta cell mass