Letter | Published:

Regulation of the glucagon receptor by physiological hyperglucagonaemia

Nature volume 272, pages 829832 (27 April 1978) | Download Citation

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Abstract

IT is well recognised that the first step in the action of polypeptide hormones and catecholamines on target cells is binding of the hormone to a membrane receptor1. Insulin2, catecholamines3 and prolactin4 have been shown to regulate the concentration of their own receptors. For example, hyperinsulinaemia due to a variety of causes is accompanied by a decrease in insulin binding5, a phenomenon which has been termed ‘down regulation’6. In contrast, prolactin has been reported to induce its own receptor4. In the case of glucagon, the effect of hyperglucagonaemia on the binding of this hormone by target cells has not been established. In starvation, hyperglucagonaemia has been associated with decreased glucagon binding7, whereas in uraemia hyperglucagonaemia has been accompanied by an increase in glucagon binding8. Since the concentrations of a variety of substrates and hormones are altered in such conditions as starvation and uraemia, the precise role of changes in circulating glucagon in mediating alterations in glucagon binding cannot be delineated from observations in starved or uraemic rats. The present study was consequently undertaken to evaluate the effects of hyperglucagonaemia induced by infusion of physiological amounts of this hormone on glucagon binding in healthy rats. Our findings demonstrate that hyperglucagonaemia lasting 5 h results in a 45% decrease in glucagon binding and a comparable decrease in glucagon-stimulated adenylate cyclase activity. These data thus provide evidence for the ‘down regulation’ of the glucagon receptor by physiological hyperglucagonaemia.

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Affiliations

  1. Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510

    • VIJAY SOMAN
    •  & PHILIP FELIG

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https://doi.org/10.1038/272829a0

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