Back to Search
Start Over
Reduced second phase insulin secretion in carriers of a sulphonylurea receptor gene variant associating with Type II diabetes mellitus.
- Source :
-
Diabetologia [Diabetologia] 2000 Apr; Vol. 43 (4), pp. 515-9. - Publication Year :
- 2000
-
Abstract
- Aims/hypothesis: The sulphonylurea receptor is a subunit of the ATP-sensitive potassium channel in the pancreatic beta cell. Mutations at nt -3 of the splice acceptor site of exon 16 and a silent mutation in exon 18 of the gene for the sulphonylurea receptor (SUR1) associate with Type II (non-insulin-dependent) diabetes mellitus in several independent populations. We investigated whether these gene variants associate with changes in the pattern of glucose-stimulated insulin secretion.<br />Methods: Subjects who had normal glucose tolerance (n = 67) and subjects with an impaired glucose tolerance (n = 94), originating from two independent studies, were included in the study. Beta-cell function and insulin sensitivity were assessed by the hyperglycaemic clamp.<br />Results: Frequencies of the exon 16 -3t allele in the normal and impaired glucose tolerant groups were 46% and 44% respectively (p = NS). The more rare exon 18 T allele showed frequencies of 5 and 7% respectively (p = NS). We observed an approximately 25% reduced second-phase insulin secretion in carriers of the exon 16 -3t allele in both groups (p < 0.05). Estimates of insulin sensitivity did not show differences between carriers and non-carriers. The variant in exon 18 and the combined presence of variants in exon 16 and exon 18 were not associated with differences in insulin secretion or insulin sensitivity in our study groups.<br />Conclusion/interpretation: The diabetes associated exon 16 -3t variant of the SUR1 gene associates with a functional change of the beta cell as reflected by reduced second-phase insulin secretion in response to a standardized hyperglycaemia in normal and impaired glucose tolerant subjects.
- Subjects :
- Aged
Blood Glucose metabolism
Diabetes Mellitus, Type 2 physiopathology
Exons
Gene Frequency
Genotype
Glucose Clamp Technique
Glucose Intolerance
Humans
Insulin pharmacology
Insulin Secretion
Islets of Langerhans metabolism
Kinetics
Middle Aged
Sulfonylurea Receptors
ATP-Binding Cassette Transporters
Diabetes Mellitus, Type 2 genetics
Insulin metabolism
Mutation
Potassium Channels genetics
Potassium Channels, Inwardly Rectifying
Receptors, Drug genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0012-186X
- Volume :
- 43
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Diabetologia
- Publication Type :
- Academic Journal
- Accession number :
- 10819247
- Full Text :
- https://doi.org/10.1007/s001250051337