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Enhanced glucose uptake into adipose tissue induced by early growth restriction augments excursions in plasma leptin response evoked by changes in insulin status

International Journal of Obesity volume 25, pages 1775–1781 (2001)Cite this article

Abstract

OBJECTIVE: The study used a rat model of moderate protein restriction exclusively during fetal and early neonatal life, which has been established to cause intrauterine early growth retardation, to investigate possible association between adipocyte glucose utilisation and leptin secretion in vivo.

DESIGN: These rats, termed early protein restricted, were transferred to a diet containing the standard amount of protein at weaning and remained on this diet til adulthood, at which time adipocyte glucose utilisation and leptin secretion was compared with that of age-matched controls. Insulin status was modulated by acute (2 h) insulin infusion at a constant rate (4.2 mU/min per kg) to elevate insulin to the high physiological range. Euglycaemia was maintained by variable glucose infusion.

MEASUREMENTS: Glucose utilisation was measured in vivo in conscious unrestrained rats using 2-deoxy[1-3H] glucose. Leptin concentrations (measured by radioimmunoassay) and whole-body glucose kinetics (measured using [3-3H] glucose) were studied in the postabsorptive state and after acute insulin stimulation.

RESULTS: Adipose-tissue glucose utilisation rates in vivo tended to be higher in the post-absorptive state and were consistently 1.8–3.0-fold higher after insulin stimulation in the early-protein-restricted group compared with the control group. Both the absolute increase in leptin concentration elicited by hyperinsulinaemia and the magnitude of the effect of insulin to elevate plasma leptin levels were greater in the early-protein-restricted group compared with the control group (by 2.2-fold and 1.6-fold, respectively). The effect of insulin to stimulate Rd was much greater in the early-protein-restricted group (4.1-fold) than in the control group (2.2-fold) and the absolute increase in Rd elicited by insulin was 43% higher in the early-protein-restricted group than in the control group.

CONCLUSIONS: It is concluded that poor early growth enhances the acute leptin response to changes in insulin status through programmed changes in adipocyte glucose handling.

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Acknowledgements

This work was supported in part by a grant from Diabetes UK (formerly the British Diabetic Association).

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  1. Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London, UK

    MJ Holness

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Correspondence to MJ Holness.

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Holness, M. Enhanced glucose uptake into adipose tissue induced by early growth restriction augments excursions in plasma leptin response evoked by changes in insulin status. Int J Obes 25, 1775–1781 (2001). https://doi.org/10.1038/sj.ijo.0801836

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