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Effects of preterm birth induced with or without exogenous glucocorticoids on the ovine glucose–insulin axis

Published online by Cambridge University Press:  15 January 2020

Amita Bansal
Affiliation:
College of Health and Medicine, ANU Medical School, The Australian National University, Canberra, ACT 2601, Australia
Jane M. Alsweiler
Affiliation:
Department of Paediatrics, Child and Youth Health, Faculty of Medical and Health Sciences, University of Auckland, Auckland1023, New Zealand
Mark H. Oliver
Affiliation:
College of Health and Medicine, ANU Medical School, The Australian National University, Canberra, ACT 2601, Australia
Anne Jaquiery
Affiliation:
College of Health and Medicine, ANU Medical School, The Australian National University, Canberra, ACT 2601, Australia
Hui Hui Phua
Affiliation:
College of Health and Medicine, ANU Medical School, The Australian National University, Canberra, ACT 2601, Australia
Mike Dragunow
Affiliation:
Centre of Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland1023, New Zealand
Rob de Matteo
Affiliation:
Department of Anatomy and Developmental Biology, Monash University, Melbourne, Australia
Jane E. Harding
Affiliation:
College of Health and Medicine, ANU Medical School, The Australian National University, Canberra, ACT 2601, Australia
Frank H. Bloomfield*
Affiliation:
College of Health and Medicine, ANU Medical School, The Australian National University, Canberra, ACT 2601, Australia
*
Address for correspondence: Frank H. Bloomfield, Liggins Institute, University of Auckland, Private Bag 92019, Auckland1142, New Zealand. Email: f.bloomfield@auckland.ac.nz

Abstract

Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11–14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12–13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml−1·kg−1·min−1·ng−1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%–71% in NG-Prem vs. G-Prem and 42%–80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.

Type
Original Article
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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Footnotes

Current address: Center for Research on Reproduction and Women’s Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

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