Sulfonylurea receptor gene 16-3 polymorphism – association with sulfonylurea or insulin treatment in type 2 diabetic subjects

摘要

Background: The presence of a complex phenotype of type 2 diabetes results from impaired insulin secretion and action, whereas the mechanism of action of sulfonylurea derivatives, most commonly used in the treatment of type 2 diabetes, is based on their ability to directly inhibit the ATP-sensitive potassium channel (KATP,), which leads to b-cell depolarization, subsequent influx of calcium and then insulin exocytosis. It has recently been demonstrated in healthy subjects that molecular variants of the gene encoding for the KATP, subunit - sulfonylurea receptor gene (SUR1) are associated with a decreased response of insulin secretion to intravenous injection of tolbutamide, a sulfonylurea derivative. In this study we tested whether a molecular variant of the SUR1 gene, 16-3t, has a different distribution in type 2 diabetic patients with early failure of sulfonylurea therapy, compared to patients treatable with sulfonylurea despite long diabetes duration.Material/Methods: The SUR1 polymorphism was genotyped in 68 type 2 diabetic patients who required insulin treatment and had known diabetes duration ≤ 5 years, compared to 99 patients receiving oral agents (sulfonylurea alone or in combination with metformin or acarbose) with known diabetes duration of at least 15 years.Results: We observed no significant differences in SUR1 16-3t genotype distributions or allele frequencies between the two examined groups.Conclusions: Our study provides evidence against a major impact of the SUR1 c16-3t polymorphism on the long-term effectiveness of therapy with sulfonylurea derivatives in type 2 diabetic patients.