Variations in insulin secretion in carriers of the E23K variant in the KIR6.2 subunit of the ATP-sensitive K(+) channel in the beta-cell.
An association between type 2 diabetes and genetic variation in the KIR6.2 gene has been reported in several populations. Based on in vitro studies with cell lines expressing the Glu(23)Lys (E23K) mutation, it was recently suggested that this mutation might result in altered insulin secretion. We have examined glucose-stimulated insulin secretion in relation to this KIR6.2 gene variant in two independent Dutch cohorts. Subjects with normal (n = 65) or impaired (n = 94) glucose tolerance underwent 3-h hyperglycemic clamps at 10 mmol/l glucose. We did not observe significant differences in first- or second-phase insulin secretion between carriers and noncarriers of the gene variant in either of the study populations (all P > 0.45). Furthermore, we found no evidence for a significant interaction with disease-associated gene variants in the sulfonylurea receptor (SUR1) gene. We conclude that the E23K mutation in the KIR6.2 gene is not associated with detectable alterations in glucose-stimulated insulin secretion in two independent populations from the Netherlands.
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D015309:Glucose Clamp Technique; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015221:Potassium Channels / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors
C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate