caa a22 4500 475772474 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s001250051484 doi (NATIONALLICENCE)springer-10.1007/s001250051484 Glucagon receptors on human islet cells contribute to glucose competence of insulin release [Elektronische Daten] [P. Huypens, Z. Ling, D. Pipeleers, F. Schuit] 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] Springer-Verlag Berlin Heidelberg, 2000 Keywords Glucagon receptors nationallicence GLP-1 receptors nationallicence GIP receptors nationallicence beta cells nationallicence cyclic AMP nationallicence insulin nationallicence diabetes nationallicence glucose competence nationallicence Huypens P. Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium, BE aut Ling Z. Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium, BE aut Pipeleers D. Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium, BE aut Schuit F. Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium, BE aut https://doi.org/10.1007/s001250051484 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051484 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Huypens P. Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium, BE aut NATIONALLICENCE 700 1- Ling Z. Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium, BE aut NATIONALLICENCE 700 1- Pipeleers D. Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium, BE aut NATIONALLICENCE 700 1- Schuit F. Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Brussels, Belgium, BE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer