title: Programming of glucose-insulin homoeostasis: long-term consequences of pre-natal versus early post-natal nutrition insults. Evidence from a sheep model.
abstract: OBJECTIVE
  Exposure to adverse intra-uterine conditions can predispose for metabolic disorders later in life. By using a sheep model, we studied (i) how programming of glucose-insulin homoeostasis during late gestation is manifested later in life depending on the early post-natal dietary exposure and (ii) whether dietary alteration in obese individuals can prevent adverse outcomes of early life programming.
  
  
  METHODS
  During late gestation, twin-pregnant sheep were fed 100% (NORM) or 50% (LOW) of energy and protein requirements. After birth, offspring were exposed to a moderate (CONV) or high-carbohydrate-high-fat (HCHF) diet until around puberty. Offspring remaining thereafter (exclusively females) were fed a moderate diet until young adulthood.
  
  
  RESULTS
  LOW lambs had increased insulin secretory responses during intravenous glucose tolerance tests indicative of reduced insulin sensitivity. HCHF lambs were hypertriglyceridaemic, 75% had mild pancreatic collagen infiltration, and their acute insulin secretory response and insulin clearance during intravenous glucose and insulin tolerance tests, respectively, were reduced. However, NORM-HCHF in contrast to LOW-HCHF lambs had normal glucose tolerance, indicating that later health outcomes are highly influenced by pre-natal nutrition. Dietary alteration normalized glucose-insulin homoeostasis in adult HCHF females, whereas late-gestation undernutrition (LOW) permanently depressed insulin sensitivity.
  
  
  CONCLUSIONS
  Maintenance of glucose tolerance in sheep exposed to pre-natal undernutrition relied on pancreatic hypersecretion of insulin to compensate for reduced insulin sensitivity. A mismatching high-fat diet in early post-natal life interfered with this pancreatic hypersecretion resulting in reduced glucose tolerance. Early post-natal, but not late pre-natal, impacts on glucose-insulin homoeostasis could be reversed by dietary correction later in life.
authors: Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors: A H
authors: AH
authors: Kongsted
authors: M P
authors: MP
authors: Tygesen
authors: S V
authors: SV
authors: Husted
authors: M H
authors: MH
authors: Oliver
authors: A
authors: A
authors: Tolver
authors: V G
authors: VG
authors: Christensen
authors: J H
authors: JH
authors: Nielsen
authors: M O
authors: MO
authors: Nielsen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D019317:Evidence-Based Medicine; D005260:Female; D006706:Homeostasis; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D044342:Malnutrition / Q000196:embryology / Q000378:metabolism*; D023421:Models, Animal; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D012756:Sheep
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: high-carbohydrate-high-fat diet; late-gestation undernutrition; obesity; pancreas