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- Title
Carriers of Risk Alleles in TCF7L2 Have Impaired Postprandial GIP Secretion and Reduced Insulin Secretion During Infusion of GLP-1.
- Authors
Pilgaard, Kasper; Schou, Jakob; Poulsen, Pernille; Jensen, Christine Bjørn; Wegner, Lise; Vilsbøll, Tina; Madsbad, Steen; Holst, Jens Juul; Vaag, Allan
- Abstract
Common polymorphisms of the transcription factor 7-like 2 gene (TCF7L2) have been associated vwith Type 2 diabetes (T2D), presumably through impaired insulin secretion. T2D is associated with defects in the secretion and action of Glucagon Like Peptide-1 (GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP). The TCF7L2 gene is a transcription factor of the proglucagon gene which encodes the insulinotropic GLP-1 in the intestine, why an effect on incretin secretion and action has been hypothesized. We aimed to assess the influence of TCFTL2 polymorphisms on incretin hormone secretion and action in young non-diabetic men (n=34) aged 24 yrs. We genotyped the rs12255372, rs7903146 and rs10885406 polymorphisms of TCF7L2. The secretion of incretin hormones and insulin was studied during a standard meal test, whereas the action of incretin hormones was studied during 2 hours hyperglycaemic (p-glucose at 7mM) clamp with infusions of GLP-1 and GIP, respectively. The GIP response during meal tests was reduced by 21% in carriers of the rs7903146 risk allele (AUC[sub GIP incr]:CT/TT: 66 (27), CC: 84 (25) pmol/l/min, p=0.05). The TCF7L2 SNPs did not influence GLP-1 secretion. During hyperglycaemic clamp we found impaired insulinotropic action of GLP-1, but not GIP, in the carriers of the rs7903146 T-allele when corrected for insulin action (AUC[sub insulin 0-120]: CT/TT: 197 (50) vs. CC: 239 (49) U ; p=0,04). In conclusion, we found reduced postprandial secretion of GIP and reduced insulinotropic action of GLP-1 to be associated with TCF7L2 polymorphisms associated with T2D in a cohort of young healthy men.
- Subjects
TRANSCRIPTION factors; PEPTIDES; INSULIN; GENETIC polymorphisms; TYPE 2 diabetes
- Publication
Diabetes, 2007, Vol 56, pA18
- ISSN
0012-1797
- Publication type
Article