Binding specificity and signal transduction of receptors for glucagon-like peptide-1(7-36)amide and gastric inhibitory polypeptide on RINm5F insulinoma cells.
Glucagon-like peptide-1(7-36)amide (GLP-1(7-36) amide) and gastric inhibitory polypeptide (GIP), peptides of the glucagon family, stimulate insulin secretion in vitro and in vivo. They possess high N-terminal sequence homology. Binding studies with 125I-labelled GIP and 125I-labelled GLP-1(7-36)amide were performed in RINm5F insulinoma cells to investigate receptor specificity and to compare both receptors directly. Both binding sites were highly ligand-specific: GIP did not bind to the GLP-1(7-36)amide receptor and vice versa. Both peptides increased intracellular cyclic AMP levels; GLP-1(7-36)amide was 100-fold more potent in stimulating cyclic AMP production when compared with GIP. At ranges of 1-10 nmol GLP-1(7-36)amide/l and 0.1-10 nmol GIP/l, corresponding to submaximal binding concentrations, the hormones showed an additive effect on cyclic AMP production. The N-terminal portion of GIP was important for binding, as GIP(1-30) showed almost full binding and biological activity. GIP(17-42) bound in a concentration-dependent manner with approximately 500-fold lower potency than GIP. At concentrations of up to 10 mumol GIP(17-42)/l no stimulation of cyclic AMP was observed.
I Department of Medicine, Christian Albrechts University, Kiel, Germany.
B
B
Gallwitz
M
M
Witt
U R
UR
Fölsch
W
W
Creutzfeldt
W E
WE
Schmidt
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D007515:Islets of Langerhans / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D018027:Receptors, Glucagon; D015398:Signal Transduction
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011964:Receptors, Gastrointestinal Hormone; D018027:Receptors, Glucagon; C061970:glucagon-like peptide 1 (7-36); D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; C041086:gastric inhibitory polypeptide receptor; D000242:Cyclic AMP