Effect of maternal undernutrition on fetal pancreatic β-cell development, growth and functionality: Involvement of the IGF system | Efecto de la subnutrición materna sobre el desarrollo, crecimiento y funcionalidad de las células β pancreáticas en el feto: Implicación del sistema de IGFs

Abstract

We have previously shown that Wistar fetuses from protein-caloric undernourished (U) pregnant rats at 21 days post coitum (dpc) exhibit increased β-cell mass and hyperinsulinemia. The metabolic and molecular processes involved in these alterations are not fully understood. To this end, we examined the immediate effects of a protein-caloric restricted diet on the mechanisms that regulate both the functionality and growth of the β-cells during fetal development. The data show that: 1) Food restriction causes in fetuses alterations in glucose-stimulated insulin secretion as a consequence of changes in the levels of insulin gene expression and content. Altered insulin mRNA expression seems to be caused by the increase in p38/SAPK2 protein levels and glucose oxidation, both of them implicated in the activation of the insulin gene transcription factor PDX-1. 2) The increased β-cell mass found in U fetuses could be related to a higher stimulation of β-cell replication, due to locally increased pancreatic IGF-1, the elevated number of IGF-1R and the enhancement in both basal and glucose/IGF-1 activations of the IRS-2/PI3K/Akt pathway.