title: Pre- and postnatal methyl deficiency in the rat differentially alters glucose homeostasis.
abstract: OBJECTIVE
  Early-life methyl-donor deficiency is implicated in growth restriction and later-life development of type 2 diabetes mellitus. We ascertained whether dietary methyl-donor deficiency in the mother during pregnancy or during postweaning growth in the rat would impair glucose homeostasis, insulin secretion and pancreatic endocrine development in young adults.
  
  
  METHODS
  Effects of maternal methyl deficiency (90% deficiency in methionine, folate and choline) were compared with those of postweaning methyl deficiency and with control diets for effects on growth, impaired glucose tolerance, insulin secretion and pancreas development in offspring. Studies focussed on male offspring, which have been shown more susceptible to early-life influences on later disease development.
  
  
  RESULTS
  Prenatal methyl deficiency delayed delivery, restricted birthweight by 22%, reduced litter size by 33% and increased offspring mortality to 23% shortly after birth. It reduced relative endocrine pancreatic mass in adult male offspring to 46% of endocrine mass in controls, but only mildly impaired their glucose tolerance and insulin secretion. In contrast, postweaning methyl deficiency restricted growth of male rats and reduced relative pancreatic endocrine mass (-40%), but improved their glucose tolerance, despite decreased insulin secretion.
  
  
  CONCLUSIONS
  It is clear that the global undernutrition (UN) during pregnancy in rodents alters glucose metabolism in adult offspring. It has been hypothesised that alterations in epigenetic mechanisms may underlie this phenotype. However, removing all methyl donors during pregnancy, which are essential for epigenetic processes in development, did not cause any alteration in glucose metabolism in offspring as seen in the global UN model.
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Greg C
authors.initials: GC
authors.lastname: Smith
authors.forename: Galina
authors.initials: G
authors.lastname: Konycheva
authors.forename: Marie A
authors.initials: MA
authors.lastname: Dziadek
authors.forename: Susan R
authors.initials: SR
authors.lastname: Ravelich
authors.forename: Selina
authors.initials: S
authors.lastname: Patel
authors.forename: Shiva
authors.initials: S
authors.lastname: Reddy
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Breier
authors.forename: Mark H
authors.initials: MH
authors.lastname: Vickers
authors.forename: Julie A
authors.initials: JA
authors.lastname: Owens
authors.forename: Lynnette R
authors.initials: LR
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002796:Choline Deficiency / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005494:Folic Acid Deficiency / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D048788:Growth and Development / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000187:drug effects / Q000502:physiology*; D008697:Methane / Q000031:analogs & derivatives / Q000494:pharmacology; D008715:Methionine / Q000172:deficiency*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar
chemical_list: C051224:methyl radical; D008715:Methionine; D005947:Glucose; D008697:Methane