title: Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of the TCF7L2 rs7903146 risk T allele.
abstract: We characterised 62 non-diabetic, middle-aged, Caucasians with and without the T risk allele of rs7903146 in transcription factor 7-like 2 (TCF7L2) with regard to secretion of insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) as well as insulin sensitivity and endogenous glucose production. All participants had a 3-h oral glucose tolerance test (OGTT), an intravenous glucose tolerance test and a euglycaemic, hyperinsulinaemic clamp. After adjustment for age and sex, risk T allele carriers had higher haemoglobin A1c levels (p = 0.030), reduced first-phase insulin response (p = 0.048), higher peripheral insulin sensitivity (p = 0.050) and lower fasting GIP concentrations (p = 0.003) than CC allele carriers. The latter was also reflected by lower total GIP secretion during the OGTT (p = 0.018). We found no significant differences in endogenous glucose production, hepatic insulin sensitivity or fasting concentrations of glucose, insulin, glucagon and GLP-1 between the groups. The findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP.
authors.forename: K
authors.initials: K
authors.lastname: Færch
authors.forename: K
authors.initials: K
authors.lastname: Pilgaard
authors.forename: F K
authors.initials: FK
authors.lastname: Knop
authors.forename: T
authors.initials: T
authors.lastname: Hansen
authors.forename: O
authors.initials: O
authors.lastname: Pedersen
authors.forename: T
authors.initials: T
authors.lastname: Jørgensen
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
mesh_terms: D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005838:Genotype; D005934:Glucagon / Q000097:blood*; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000097:blood*; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics*
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon