Diabetologia

, Volume 43, Issue 8, pp 1012–1019 | Cite as

Glucagon receptors on human islet cells contribute to glucose competence of insulin release

  • P. Huypens
  • Z. Ling
  • D. Pipeleers
  • F. Schuit
Article

Abstract

Aims/hypothesis. Synergism between glucose and cAMP in the stimulation of insulin secretion has been suggested to regulate beta cells. This study assessed the importance of an interaction between glucose and cAMP in the stimulation of insulin secretion from human islet cells by investigating expression and functional activity of receptors recognising glucagon, glucagon-like peptide-1 (7–36)amide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Methods. Expression of the glucagon, GLP-1 and GIP receptors in human islets was investigated by northern blots and reverse transcription-polymerase chain reaction analysis. Functional activity of these receptors was assessed by the effects of peptides (agonists and antagonists) on glucose-induced insulin release. Results. Human islet cells express transcripts encoding glucagon, GLP-1 and GIP receptors. Glucose (10 mmol/l) stimulated insulin release 4.5 ± 0.6-fold over basal (2.5 mmol/l). This glucose effect was amplified by 10 nmol/l GLP-1, GIP or glucagon. It was reduced by 51 ± 6 % in the presence of 1 μmol/l of the glucagon-receptor antagonist des-His1-[Glu9]-glucagon-amide (n = 8; p < 0.05), indicating participation of endogenously released glucagon in the process of glucose-induced insulin release. The glucagon-receptor antagonist also suppressed the potentiation of glucose-induced insulin release by addition of 10 nmol/l glucagon. Conclusion/interpretation. These data suggest that human beta cells express functional glucagon receptors which can, similar to incretin hormone receptors, generate synergistic signals for glucose-induced insulin secretion. [Diabetologia (2000) 43: 1012–1019]

Keywords Glucagon receptors GLP-1 receptors GIP receptors beta cells cyclic AMP insulin diabetes glucose competence 

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • P. Huypens
    • 1
  • Z. Ling
    • 1
  • D. Pipeleers
    • 1
  • F. Schuit
    • 1
  1. 1.Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, BelgiumBE

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