Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells

摘要: The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are factors released from the small intestine to blood stream in response oral glucose ingestion. effect of GLP-1 is maintained patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, GIP diminished or lacking. We defined exon-intron boundaries human receptor, made a mutational analysis gene identified amino acid substitutions, A207 V E354Q. In an association study 227 Caucasian diabetic 224 matched tolerant control subjects, allelic frequency polymorphism was 1.1 % 0.7 subjects (p = 0.48), whereas codon 354 24.9 versus 23.2 subjects. Interestingly, (6 population) who were homozygous variant had on average 14 decrease fasting serum C-peptide concentration 0.01) 11 same variable 30 min after load 0.03) compared wild-type receptor. Investigation function receptor variants Chinese hamster fibroblasts showed, however, that GIP-induced cAMP formation binding cells expressing receptors not different findings conclusion, associated random Danish origin altered production when stably transfected fibroblasts. finding between homozygosity reduced post tolerance test (OGTT) concentrations, calls further investigations could suggest even state regulates beta-cell secretory response. [Diabetologia (1998) 41: 1194–1198]