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Effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics in young adult horses

Published online by Cambridge University Press:  20 December 2016

O. A. Valenzuela ,
J. K. Jellyman ,
V. L. Allen ,
N. B. Holdstock ,
A. J. Forhead  and
A. L. Fowden
O. A. Valenzuela
Affiliation:
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
J. K. Jellyman
Affiliation:
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
V. L. Allen
Affiliation:
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
N. B. Holdstock
Affiliation:
Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
A. J. Forhead
Affiliation:
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
A. L. Fowden*
Affiliation:
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
*
*Address for correspondence: A. L. Fowden, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK. (Email [email protected])
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Abstract

In several species, adult metabolic phenotype is influenced by the intrauterine environment, often in a sex-linked manner. In horses, there is also a window of susceptibility to programming immediately after birth but whether adult glucose–insulin dynamics are altered by neonatal conditions remains unknown. Thus, this study investigated the effects of birth weight, sex and neonatal glucocorticoid overexposure on glucose–insulin dynamics of young adult horses. For the first 5 days after birth, term foals were treated with saline as a control or ACTH to raise cortisol levels to those of stressed neonates. At 1 and 2 years of age, insulin secretion and sensitivity were measured by exogenous glucose administration and hyperinsulinaemic–euglycaemic clamp, respectively. Glucose-stimulated insulin secretion was less in males than females at both ages, although there were no sex-linked differences in glucose tolerance. Insulin sensitivity was greater in females than males at 1 year but not 2 years of age. Birth weight was inversely related to the area under the glucose curve and positively correlated to insulin sensitivity at 2 years but not 1 year of age. In contrast, neonatal glucocorticoid overexposure induced by adrenocorticotropic hormone (ACTH) treatment had no effect on whole body glucose tolerance, insulin secretion or insulin sensitivity at either age, although this treatment altered insulin receptor abundance in specific skeletal muscles of the 2-year-old horses. These findings show that glucose–insulin dynamics in young adult horses are sexually dimorphic and determined by a combination of genetic and environmental factors acting during early life.

Keywords

glucose toleranceinsulin sensitivityneonatal glucocorticoid overexposureprogramming
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 2 , April 2017 , pp. 206 - 215
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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