title: Variations in insulin secretion in carriers of gene variants in IRS-1 and -2.
abstract: Associations between type 2 diabetes (and/or parameters contributing to glucose homeostasis) and genetic variation in the genes encoding insulin receptor substrate (IRS)-1 and -2 have been reported in several populations. Recently, it has been reported that the Gly(972)Arg variant in IRS-1 was associated with reduced insulin secretion during hyperglycemic clamps in German subjects with normal glucose tolerance. We have examined glucose-stimulated insulin secretion in relation to gene variants in the IRS-1 (Gly(972)Arg) and IRS-2 (Gly(1057)Asp) genes in two Dutch cohorts. Subjects with normal (n = 64) or impaired (n = 94) glucose tolerance underwent 3-h hyperglycemic clamps at 10 mmol/l glucose. All subjects were genotyped for the IRS-1 and IRS-2 variants by PCR-RFLP--based methods. We did not observe any significant difference in both first- and second-phase insulin secretion between carriers and noncarriers of both gene variants, nor was there evidence for an association with other diabetes-related parameters. We conclude that the common gene variants in IRS-1 and IRS-2 are not associated with altered glucose-stimulated insulin secretion in two populations from the Netherlands.
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Leen M
authors.initials: LM
authors.lastname: 't Hart
authors.forename: Giel
authors.initials: G
authors.lastname: Nijpels
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
authors.forename: J Antonie
authors.initials: JA
authors.lastname: Maassen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.forename: Timon W
authors.initials: TW
authors.lastname: van Haeften
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005947:Glucose / Q000494:pharmacology; D015309:Glucose Clamp Technique; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D000078790:Insulin Secretion; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D010750:Phosphoproteins / Q000235:genetics*
chemical_list: D001786:Blood Glucose; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D005947:Glucose