Programming of glucose-insulin homoeostasis: long-term consequences of pre-natal versus early post-natal nutrition insults. Evidence from a sheep model

Acta Physiol (Oxf). 2014 Jan;210(1):84-98. doi: 10.1111/apha.12080. Epub 2013 Mar 22.

Abstract

Aim: 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.

Conclusion: 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.

Keywords: high-carbohydrate-high-fat diet; late-gestation undernutrition; obesity; pancreas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Blood Glucose / metabolism*
  • Evidence-Based Medicine
  • Female
  • Homeostasis
  • Insulin / blood*
  • Insulin Resistance
  • Malnutrition / embryology
  • Malnutrition / metabolism*
  • Models, Animal
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Sheep

Substances

  • Blood Glucose
  • Insulin