Fetal pancreatic b-cell growth and insulin-like growth factors relationship in undernourished rats

Abstract

[Background and Aims] We have previously shown that Wistar fetuses from protein- caloric undernourished pregnant rats (U) at 21 days post coitum (dpc) exhibit increased β cell-mass. This alteration is correlated with increased insulinemia and total pancreatic insulin content, a pattern reminiscent to that reported in infants of mild diabetic mothers. Both Insulinlike Growth Factor (IGF)-I and -2 are essential players for growth and development during the fetal period. The aim of the present study was to investigate in the U fetuses at 21 dpc: 1) serum IGFs levels, 2) IGFs gene expression in the liver and pancreas, and 3) in vitro mitogenic effect of IGFs in isolated fetal islets using BrdU labelling index (LI). All values were compared to those in Wi star control fetuses (C). [Methods] Serum concentrations of IGF-I and IGF-2 were measured by radioimmuno assay and radioreceptor assay respectively. RNase protection assay was performed using RNA from pancreas and liver to evaluate IGFs or IGFBPs gene expression in both tissues. [Results] Similar serum IGF-I and-2levels were observed in U and C. IGF-I and IGF-2 mRNAs were detected in liver and pancreas of both C and U fetuses. Despite being decreased in the liver, IGF-l mRNA level was increased in U pancreases as compared to C. Concerning IGF-2 gene expression it was diminished in U pancreas while being normal in the liver as compared to C. No difference in IGFBP-I, -2 and -3 mRNA levels was detected in U liver when compared to C. However, gene expression of IGFBP-2 was increased and that of IGFBP-3 was decreased in U pancreases. Finally, the in vitro study showed a normal BrdU LI in U isolated fetal islets under basal conditions while it was found significantly increased twice in response to both IGF-I and IGF-2 (lOOng/ml) as compared to fetal C islets. [Conclusion] Our data suggest that in U fetuses at 21 dpc: I) the increased β-cell mass can be related to the stimulation of replicative β-cell response due to locally increased IGF-I in the pancreas 2) such IGF-I action is perhaps favored by an enhanced IGFBP-2 gene expression in pancreas, and 3) at variance with previous reports in several models of decreased intrapancreatic IGF-2 expression in fetuses, the low IGF-2 mRNA level as it is observed in the present U model does not correlate with a decreased β-cell growth.