title: Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men.
abstract: We investigated the association of glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes with amino acid levels in the population-based Metabolic Syndrome in Men (METSIM) Study, including 9,369 nondiabetic or newly diagnosed type 2 diabetic Finnish men. Plasma levels of eight amino acids were measured with proton nuclear magnetic resonance spectroscopy. Increasing fasting and 2-h plasma glucose levels were associated with increasing levels of several amino acids and decreasing levels of histidine and glutamine. Alanine, leucine, isoleucine, tyrosine, and glutamine predicted incident type 2 diabetes in a 4.7-year follow-up of the METSIM Study, and their effects were largely mediated by insulin resistance (except for glutamine). We also found significant correlations between insulin sensitivity (Matsuda insulin sensitivity index) and mRNA expression of genes regulating amino acid degradation in 200 subcutaneous adipose tissue samples. Only 1 of 43 risk single nucleotide polymorphisms for type 2 diabetes or hyperglycemia, the glucose-increasing major C allele of rs780094 of GCKR, was significantly associated with decreased levels of alanine and isoleucine and elevated levels of glutamine. In conclusion, the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia, reflecting, at least in part, insulin resistance. Only one single nucleotide polymorphism regulating hyperglycemia was significantly associated with amino acid levels.
authors.affiliation: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Alena
authors.initials: A
authors.lastname: Stancáková
authors.forename: Mete
authors.initials: M
authors.lastname: Civelek
authors.forename: Niyas K
authors.initials: NK
authors.lastname: Saleem
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.forename: Henna
authors.initials: H
authors.lastname: Cederberg
authors.forename: Jussi
authors.initials: J
authors.lastname: Paananen
authors.forename: Jussi
authors.initials: J
authors.lastname: Pihlajamäki
authors.forename: Lori L
authors.initials: LL
authors.lastname: Bonnycastle
authors.forename: Mario A
authors.initials: MA
authors.lastname: Morken
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.forename: Päivi
authors.initials: P
authors.lastname: Pajukanta
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000273:Adipose Tissue / Q000378:metabolism; D000368:Aged; D000596:Amino Acids / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D005387:Finland; D005786:Gene Expression Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000596:Amino Acids; D001786:Blood Glucose; C485100:GCKR protein, human