HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weisnagel, S. J. Articles by Bouchard, C. Search for Related Content PubMed PubMed Citation Articles by Weisnagel, S. J. Articles by Bouchard, C. Social Bookmarking                What's this?

Decreased Fasting and Oral Glucose Stimulated C-peptide in Nondiabetic Subjects With Sequence Variants in the Sulfonylurea Receptor 1 Gene

¹ Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Québec, Canada
² Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana
³ Diabetes Research Unit, Laval University Health Center, Ste-Foy, Québec, Canada
⁴ Division of Biostatistics and Departments of Psychiatry and Genetics, Washington University Medical School, St. Louis, Missouri

The high-affinity sulfonylurea receptor 1 (SUR1) plays an important role in regulating insulin secretion. In the Québec Family Study, we genotyped 731 individuals (685 nondiabetic [ND] subjects) for the SUR1 gene IVS15-3ct and exon 18 Thr759(ACCACT) polymorphisms using polymerase chain reaction–restriction fragment-length polymorphism analysis. Phenotypes measured were fasting plasma glucose (GLU), fasting plasma insulin (INS), and fasting C-peptide (CPEP), as well as oral glucose tolerance test (OGTT) responses; they were adjusted for age, sex, waist circumference, and the sum of six skinfold thicknesses. In ND subjects, exon 18 Thr759(ACCACT) T allele carriers (T⁺) had lower CPEP (P = 0.022, -12.8%) and acute C-peptide responses (area above basal in first 30 min [CP30]) (P = 0.051, -12.4%) than noncarriers (T^–). Also, in those with the cT/tC haplotype (from both IVS15-3ct and exon 18 Thr759[ACCACT] polymorphisms), CPEP (P = 0.005, -21.2%), CP30 (P = 0.034, -19.2%), and total C-peptide responses (P = 0.016, -20.2%) were lower than that in cT^– subjects. In overweight individuals (BMI >25 kg/m²), differences between carriers and noncarriers of the T or cT alleles were greater for GLU (P = 0.023–0.034), CPEP (P = 0.021–0.015), acute OGTT insulin response (P = 0.014–0.019), and CP30 (P = 0.034–0.019). These results suggest that the T and cT allele variants are associated with lower insulin secretion parameters, particularly in female and overweight subjects, adding evidence to the role of SUR1 sequence variants in decreased insulin secretion.

Abbreviations: CP30, OGTT C-peptide area above basal in first 30 min; CPEP, fasting plasma C-peptide; CPtot, OGTT C-peptide area above basal over 180 min; GLU, fasting plasma glucose; IN30, OGTT insulin area above basal in first 30 min; INS, fasting plasma insulin; IRI, immunoreactive insulin; ND, nondiabetic; OGTT, oral glucose tolerance test; PCR, polymerase chain reaction; PI, proinsulin; QFS, Québec Family Study; SF6; sum of six skinfold thicknesses; SUR1, sulfonylurea receptor 1; WC, waist circumference

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. O. Kilpelainen, T. A. Lakka, D. E. Laaksonen, O. Laukkanen, J. Lindstrom, J. G. Eriksson, T. T. Valle, H. Hamalainen, S. Aunola, P. Ilanne-Parikka, et al. Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes Physiol Genomics, October 19, 2007; 31(2): 264 - 272. [Abstract] [Full Text] [PDF]