Effects of nutritional supplementation of neonatal lambs on the pancreas post weaning

Abstract

mall size at birth, consequent upon preterm birth or intrauterine growth restriction, is associated with increased risk of disease in adult life. Babies born small frequently receive nutritional supplementation to improve growth. It is uncertain whether the relationship between small size at birth and long term health risk is due to size at birth per se, the accelerated postnatal growth that often follows, or the postnatal nutrition given to optimise growth. We recently found that nutritional supplementation for the first two weeks of life in healthy term lambs altered insulin secretion post weaning in a sexspecific manner and independent of postnatal growth. The hypothesis of this thesis was that the altered insulin secretion was due to effects on pancreatic gene expression and cell development. The specific aims were to measure the expression of genes involved in cell development and insulin secretion and those involved in insulin action on the liver, and to assess pancreatic islet morphology. Tissues were collected at 4 months of age from term singleton lambs randomly assigned to a nutritional supplement analogous to human breast milk fortifier (supplement, n=11) or ewe milk alone (control, n=9) for the first two weeks of life. mRNA levels were measured by real time PCR, pancreatic insulin concentration by radioimmunoassay and cell morphology was assessed by immunofluorescent histochemistry. In supplemented males, mRNA levels of pancreatic genes involved in cell development (Pdx-1, IGF-1, and IGF-2) and insulin secretion (GLUT2, glucokinase, and insulin) were upregulated by 20-120% (p<0.01) compared with control males. In contrast, in supplemented females mRNA levels of these genes were downregulated 5-36% (p<0.01). Pancreatic insulin content and cell mass (preliminary data only) followed similar patterns. In the liver, supplementation increased mRNA levels of phosphoenolpyruvate carboxykinase in both sexes iii (p<0.05) whereas mRNA levels of peroxisome proliferator-activated receptorwere decreased in males only (p<0.05). In conclusion, brief nutritional supplementation in healthy term lambs alters pancreatic gene expression and insulin secretion four months later. Changes were sex-specific and have the potential to affect glucose tolerance in later life. Whether nutritional intervention may affect later pancreatic function in babies warrants investigation.