Molecular adaptations in islets from neonatal rats reared artificially on a high carbohydrate milk formula

Four day-old rat pups artificially raised on a high carbohydrate (HC) milk formula during their suckling period immediately develop hyperinsulinemia w hich persists into adulthood despite weaning onto lab chow on day 24. The p resent study investigates the molecular adaptations in islets isolated from neonatal rats in response to this dietary treatment during their suckling period. There is a significant increase in the level of preproinsulin mRNA and insulin biosynthesis in 12 day-old HC islets compared to islets from ag e-matched mother-fed (MF) control rats. Pancreatic duodenal homeobox factor -1 (PDX-1) modulates pancreatic ontogeny as well as preproinsulin gene expr ession in islets from neonatal rats. The mRNA level. DNA binding activity a nd protein content of PDX-1 are significantly increased in HC islets. The s tress-activated protein kinase-2 and phosphatidylinositol 3-kinase have bee n reported to modulate PDX-1 activity in islets. The mRNA levels of these k inases are increased in HC islets. The mRNA level of upstream stimulatory f actor (a modulator of PDX-1 gene expression) is also significantly increase d in HC islets. These results indicate that the upregulation of several mol ecular events, including increases in the gene expression of preproinsulin, transcription factors and kinases may contribute to the chronic hyperinsul inemic state in the HC rats. (C) 2001 Elsevier Science Inc. All rights rese rved.