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

Aims/hypothesis. Synergism between glucose and cAMP in the stimulation of i nsulin secretion has been suggested to regulate beta cells. This study asse ssed the importance of an interaction between glucose and cAMP in the stimu lation of insulin secretion from human islet cells by investigating express ion and functional activity of receptors recognising glucagon, glucagon-lik e peptide-1 (7-36)amide (GLP-1) and glucose-dependent insulinotropic polype ptide (GLP). Methods. Expression of the glucagon, GLP-1 and GIP receptors in human islet s was investigated by northern blots and reverse transcription-polymerase c hain reaction and analysis. Functional activity of these receptors was asse ssed by the effects of peptides (agonists and antagonists) on glucose-induc ed 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 mu mol/l of the glucagon-receptor antagonist des-His(1)-[Glu9]-glucagon-amide (n = 8; p < 0.05), indicating participation of endogenously released gluca gon in the process of glucose-induced insulin release. The glucagon-recepto r antagonist also suppressed the potentiation of glucose-induced insulin re lease 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 recep tors, generate synergistic signals for glucose-induced insulin secretion.