Decreased fasting and oral glucose stimulated C-peptide in nondiabetic subjects with sequence variants in the sulfonylurea receptor 1 gene.

Abstract

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 IVS15-3c-->t and exon 18 Thr759(ACC-->ACT) 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(ACC-->ACT) 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 IVS15-3c-->t and exon 18 Thr759[ACC-->ACT] 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.

• Authors: S J Weisnagel, T Rankinen, A Nadeau, D C Rao, Y C Chagnon, L Pérusse, C Bouchard
• Journal: Diabetes (Diabetes) Vol. 50 Issue 3 Pg. 697-702 (Mar 2001) ISSN: 0012-1797 [Print] United States
• PMID: 11246895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCC8 protein, human
• ATP-Binding Cassette Transporters
• Blood Glucose
• C-Peptide
• Insulin
• Potassium Channels
• Potassium Channels, Inwardly Rectifying
• Receptors, Drug
• Sulfonylurea Receptors
• Glucose

Topics

• ATP-Binding Cassette Transporters
• Administration, Oral
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Alleles
• Blood Glucose (analysis)
• Body Mass Index
• C-Peptide (blood)
• Fasting (blood)
• Female
• Genetic Variation
• Glucose (pharmacology)
• Heterozygote
• Humans
• Insulin (blood)
• Male
• Middle Aged
• Polymorphism, Genetic
• Potassium Channels (genetics)
• Potassium Channels, Inwardly Rectifying
• Receptors, Drug (genetics)
• Reference Values
• Sulfonylurea Receptors