Glucagon receptors on human islet cells contribute to glucose competence of insulin release.
OBJECTIVE
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 micromol/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.


CONCLUSIONS
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.
Huypens
P
P
Diabetes Research Centre, Faculty of Medicine, Vrije Universiteit Brussel, Belgium.
Ling
Z
Z
Pipeleers
D
D
Schuit
F
F
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D005934:Glucagon / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000502:physiology; D018027:Receptors, Glucagon / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; D005934:Glucagon; C041086:gastric inhibitory polypeptide receptor; D000242:Cyclic AMP; D005947:Glucose