%0 Journal Article
%T The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load
%A Malene Hornbak
%A Karina Banasik
%A Johanne M Justesen
%A Nikolaj T Krarup
%A Camilla H Sandholt
%A £¿sa Andersson
%A Annelli Sandb£¿k
%A Torsten Lauritzen
%A Charlotta Pisinger
%A Daniel R Witte
%A Thorkild IA S£¿rensen
%A Oluf Pedersen
%A Torben Hansen
%J BMC Medical Genetics
%D 2011
%I BioMed Central
%R 10.1186/1471-2350-12-4
%X The variants were genotyped using KASPar£¿ PCR SNP genotyping system and investigated for associations with estimates of insulin release and insulin sensitivity following an oral glucose tolerance test (OGTT) in a random sample of middle-aged Danish individuals (nACADS = 4,324; nACADM = 4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (nACADS = 8,313; nACADM = 8,344).In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (¦Â) = -3.8% (-6.3%;-1.3%), P = 0.003), reduced incremental area under the insulin curve (¦Â = -3.6% (-6.3%;-0.9%), P = 0.009), reduced acute insulin response (¦Â = -2.2% (-4.2%;0.2%), P = 0.03), and with increased insulin sensitivity ISIMatsuda (¦Â = 2.9% (0.5%;5.2%), P = 0.02). The C-allele did not associate with two other measures of insulin sensitivity or with a derived disposition index. The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, P = 0.21). rs11161510 of ACADM did not associate with any indices of glucose-stimulated insulin release or with T2D.In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS was associated with reduced measures of glucose-stimulated insulin release during an OGTT, a finding which in part may be mediated through an impaired ¦Â-oxidation of fatty acids.Acute exposure of free fatty acids (FFA) to the pancreatic ¦Â-cells is known to both stimulate insulin secretion and modulate the glucose-stimulated insulin secretion (GSIS) whereas chronic exposure leads to desensitization of the insulin receptors and decreased function of the pancreatic ¦Â-cells. Also, chronic exposure to FFA is associated with insulin resistance and increased risk of developing diabetes mellitus [1-9].Recently, Gieger et al. (2008) conducted a genome-wide association study (GWAS) in 284 healthy men characterized by quantitative measure
%U http://www.biomedcentral.com/1471-2350/12/4