title: Cyclic AMP production and insulin releasing activity of synthetic fragment peptides of glucose-dependent insulinotropic polypeptide.
abstract: Synthetic fragment peptides of glucose-dependent insulinotropic polypeptide (GIP) were evaluated for their ability to elevate cellular cAMP production and stimulate insulin secretion. In GIP receptor transfected CHL cells, GIP(4-42) and GIP(17-30) dose-dependently inhibited GIP-stimulated cAMP production (40 +/- 8%; p<0.01 and 15 +/- 6%; p<0.05, respectively), while GIP(1-16) exerted very weak agonist effects on cAMP production. In the clonal pancreatic beta-cell line, BRIN-BD11, GIP(1-16) demonstrated weak insulin releasing activity compared with native GIP. In contrast, GIP(4-42) and GIP (17-30) weakly antagonized the insulin releasing activity of the native peptide (23 +/- 6%; p<0.05 and 11 +/- 3%, respectively). These data demonstrate the critical role of the N-terminus and the involvement of regions of the C-terminal domain in generating full biological potency of GIP.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, BT52 ISA, UK. va.gault@ulster.ac.uk
authors.forename: V A
authors.initials: VA
authors.lastname: Gault
authors.forename: P
authors.initials: P
authors.lastname: Harriott
authors.forename: P R
authors.initials: PR
authors.lastname: Flatt
authors.forename: F P M
authors.initials: FP
authors.lastname: O'Harte
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism* / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*
chemical_list: D007328:Insulin; D010446:Peptide Fragments; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor; D000242:Cyclic AMP; D005947:Glucose