caa a22 4500 475772407 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s001250051337 doi (NATIONALLICENCE)springer-10.1007/s001250051337 Reduced second phase insulin secretion in carriers of a sulphonylurea receptor gene variant associating with Type II diabetes mellitus [Elektronische Daten] [L. M. 't Hart, J. M. Dekker, T. W. van Haeften, J. B. Ruige, C. D. A. Stehouwer, D. W. Erkelens, R. J. Heine, J. A. Maassen] 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.¶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.¶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.¶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. [Diabetologia (2000) 43: 515-519] Springer-Verlag Berlin Heidelberg, 2000 Keywords Type II diabetes mellitus, sulphonylurea receptor, genetics, insulin, beta cell, insulin secretion, impaired glucose tolerance, hyperglycaemic clamp nationallicence 't Hart L. M. Leiden University Medical Centre, Department of Molecular Cell Biology, Leiden, The Netherlands, NL aut Dekker J. M. Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, NL aut van Haeften T. W. Department of Internal Medicine, Utrecht University, Utrecht, The Netherlands, NL aut Ruige J. B. Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, NL aut Stehouwer C. D. A. Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, NL aut Erkelens D. W. Department of Internal Medicine, Utrecht University, Utrecht, The Netherlands, NL aut Heine R. J. Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, NL aut Maassen J. A. Leiden University Medical Centre, Department of Molecular Cell Biology, Leiden, The Netherlands, NL aut https://doi.org/10.1007/s001250051337 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051337 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- 't Hart L. M. Leiden University Medical Centre, Department of Molecular Cell Biology, Leiden, The Netherlands, NL aut NATIONALLICENCE 700 1- Dekker J. M. Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, NL aut NATIONALLICENCE 700 1- van Haeften T. W. Department of Internal Medicine, Utrecht University, Utrecht, The Netherlands, NL aut NATIONALLICENCE 700 1- Ruige J. B. Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, NL aut NATIONALLICENCE 700 1- Stehouwer C. D. A. Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, NL aut NATIONALLICENCE 700 1- Erkelens D. W. Department of Internal Medicine, Utrecht University, Utrecht, The Netherlands, NL aut NATIONALLICENCE 700 1- Heine R. J. Institute for Research in Extramural Medicine, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, NL aut NATIONALLICENCE 700 1- Maassen J. A. Leiden University Medical Centre, Department of Molecular Cell Biology, Leiden, The Netherlands, NL aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer