title: Brief neonatal nutritional supplementation has sex-specific effects on glucose tolerance and insulin regulating genes in juvenile lambs.
abstract: The nutritional plane and composition during fetal life can impact upon growth and epigenetic regulation of genes affecting pancreatic β-cell development and function. However, it is not clear whether β-cell development can be altered by nutritional factors or growth rate after birth. We therefore investigated the effect of neonatal nutritional supplements on growth, glucose tolerance, and pancreatic development in lambs.
  
  
  
  Newborn lambs were randomized to daily nutritional supplements, calculated to increase macronutrient intake to a similar degree as human breast milk fortifier, or an equivalent volume of water, for 2 wk while continuing to suckle ewe milk. Intravenous glucose tolerance test (IVGTT) was performed at 4 mo of age, and pancreata collected for molecular analysis.
  
  
  
  Supplemented lambs had slower weight gain than controls. In supplemented lambs, insulin response to IVGTT was increased in males but decreased in females, compared to same sex controls, and was unrelated to growth rate. mRNA expression of key genes in β-cell development showed sexually dimorphic effects. Epigenetic change occurred in the promotor region of PDX1 gene with decreased suppression and increased activation marks in supplemented lambs of both sexes.
  
  
  
  Nutritional interventions in early life have long-term, sex-specific effects on pancreatic function.
authors.affiliation: The Liggins Institute, University of Auckland, Auckland, New Zealand.|Gravida, Centre for Growth and Development, University of Auckland, Auckland, New Zealand.|Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Jaquiery
authors.affiliation: The Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Sharon S
authors.initials: SS
authors.lastname: Park
authors.affiliation: The Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Hui Hui
authors.initials: HH
authors.lastname: Phua
authors.affiliation: The Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Berry
authors.affiliation: The Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Daphne
authors.initials: D
authors.lastname: Meijler
authors.affiliation: The Liggins Institute, University of Auckland, Auckland, New Zealand.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Harding
authors.affiliation: The Liggins Institute, University of Auckland, Auckland, New Zealand.|Gravida, Centre for Growth and Development, University of Auckland, Auckland, New Zealand.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Oliver
authors.affiliation: The Liggins Institute, University of Auckland, Auckland, New Zealand.|Gravida, Centre for Growth and Development, University of Auckland, Auckland, New Zealand.|Department of Paediatrics: Child and Youth Health, University of Auckland, Auckland, New Zealand.
authors.forename: Frank H
authors.initials: FH
authors.lastname: Bloomfield
mesh_terms: D000821:Animal Feed; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D019587:Dietary Supplements; D044127:Epigenesis, Genetic; D005260:Female; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D008892:Milk; D010179:Pancreas / Q000254:growth & development / Q000502:physiology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012727:Sex Characteristics; D034561:Sheep, Domestic / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics; D015430:Weight Gain
chemical_list: D051273:Glucose Transporter Type 2; D018398:Homeodomain Proteins; D007328:Insulin; D012333:RNA, Messenger; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D007335:Insulin-Like Growth Factor II