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1 School of Human Development, University Hospital, Centre for Reproduction and Early Life, Nottingham, United Kingdom
2 Department of Clinical Biochemistry, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom
3 School of Nursing, University of Nottingham, Mansfield, United Kingdom
4 Department of Animal Sciences, University of Missouri, Columbia, Missouri, USA
* To whom correspondence should be addressed. E-mail: david.gardner{at}nottingham.ac.uk.
The present study examines the effects of late vs. early gestation undernutrition on adult glucose-insulin homeostasis in sheep, and investigates whether the lower birth weight of twins alters glucose-insulin handling in adult life. Pregnant sheep were fed to requirement (100% intake) from day 0 of gestation to term (~147 dGA, control singles [CS] n=5; control twins [CT] n=5) or to 50% requirement from day 0-30 dGA (NRE, n=5) or day 110-term (NRL, n=4). At all other times NR sheep received 100% intake. All sheep lambed naturally; offspring were weaned at 10 weeks, and reared on pasture until 1 year of age. At this time, indwelling catheters were inserted and 2-4 days later basal metabolic and endocrine status and responses to an IVGTT and feeding were assessed. Adipose and skeletal muscle were then sampled after humane euthanasia and analysed for expression of insulin signalling proteins and GLUT4. Between groups, birth weight of singletons was similar and increased relative to twins. At one year of age, weights were similar between groups. The AUC for glucose and insulin during the IVGTT were greater in NRL vs. other groups, indicating glucose intolerance. This was associated with reduced adipose, but not muscle, GLUT4 and increased adipose tissue mass. Adult glucose-insulin homeostasis in sheep was unaffected by fetal number. In conclusion prenatal undernutrition, specifically during late gestation, affects adult offspring intermediary metabolism, in particular, glucose-insulin homeostasis.
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