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J Biol Regul Homeost Agents. 2018 May-Jun;32(3):465-478.

The role for cyclic Glycine-Proline, a biological regulator of insulin-like growth factor-1 in pregnancy-related obesity and weight changes.

Author information

1
Department Pharmacology and Clinical Pharmacology, School of Medical Sciences, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand.
2
Centre for Brain Research, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand.
3
Brain Research New Zealand, New Zealand.
4
The Liggins Institute, University of Auckland, Auckland, New Zealand.
5
AgResearch Ltd, Ruakura Research Centre, Hamilton, New Zealand.
6
Riddet Institute, University of Massey, Palmerston North, New Zealand.
7
Department of Paediatrics, Child and Youth Health, School of Medicine, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand
8
Department of O&G, School of Medicine, Faculty of Medicine and Health Sciences, University of Auckland, Auckland, New Zealand
9
Department of Medicinal Chemistry, School of Chemistry, University of Auckland, Auckland, New Zealand
10
Department of Medicine, School of Medicine, University of Auckland, Auckland, New Zealand

Abstract

Cyclic Glycine-Proline (cGP) regulates the homeostasis of insulin-like growth factor (IGF)-1 function and cGP/IGF-1 ratio determines IGF-1 bioactivity in vitro and in vivo. Plasma IGF-1 represents largely inactive IGF-1 and weakly associated with human obesity and hypertension. We evaluated the regulatory role for cGP in pregnancy-related obesity and hypertension, and in obesity status between pregnancy and postpartum. Women were recruited in their first pregnancy. A cross-sectional study compared plasma concentration of cGP, IGF-1 and IGF binding protein (IGFBP)-3 in women with obesity and/or hypertension to normal controls 6-year postpartum using UPLC-MS and ELISA. A longitudinal study compared the changes of these peptides from 15-week gestation to 6-year post-partum in the women who remained normal weight, remained obese or changed to obese or to normal respectively. Study 1 is a cross-sectional study. The obese group had lower IGF-1(p = 0.001), higher cGP/IGF-1 ratio (p = 0.0055) and the hypertensive group had lower IGFBP-3 (p = 0.046) and cGP (p = 0.043) than the controls. Study 2 is a longitudinal study. Women with weight loss had increased cGP/IGF-1 ratio (p = 0.0026) and decreased IGFBP-3 (p = 0.0001) compared with women whose weight remained normal. Women with weight gain had lower IGFBP-3 (p less than 0.0001) only. Women who remained obese had increased cGP/IGF-1 ratio (p = 0.006) only. Increase in cGP/IGF-1 ratio is associated with obesity, but not hypertension. Changes of IGFBP-3 and/or cGP/IGF-1 ratio are associated with weight changes. The data suggest the role for cGP in obesity through autocrine regulation of IGF-1.

PMID:
29921371
[Indexed for MEDLINE]

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