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A serine/alanine polymorphism in the nucleotide‐binding fold‐2 of the sulphonylurea receptor‐1 (S1369A) is associated with enhanced glucose‐induced insulin secretion during pregnancy
Author(s) -
Krugluger W.,
Festa A.,
Shnawa N.,
Bucher J.,
BoltzNitulescu G.,
Schernthaner G.,
Hopmeier P.
Publication year - 2000
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1005630912875
Subject(s) - endocrinology , medicine , alanine , serine , secretion , receptor , insulin , pregnancy , chemistry , biology , genetics , biochemistry , amino acid , enzyme
The sulphonylurea receptor‐1 (SUR‐1) regulates glucose‐induced insulin secretion by controlling K + ‐ATP channel activity of the pancreatic β‐cell membrane. In this study, we investigated the putative role of a T/G‐polymorphism (exon 33, codon 1369; S1369A) in the adenosine diphosphate‐sensing nucleotide‐binding fold‐2 (NBF‐2) of the SUR‐1 on glucose‐induced insulin secretion during an oral glucose tolerance test in pregnant women (PW; n =182). Compared to PW with the T/T genotype, statistically significant elevated C‐peptide concentrations were found 60 min after glucose intake in PW with the T/G and G/G genotype (T/T 9.0±0.4 ng/ml vs T/G 10.8±0.4 ng/ml or G/G 10.8±0.7 ng/ml, p =0.01). Furthermore, compared to PW with T/T genotype the ΔC‐peptide (60/0 min) was significantly enhanced in PW with T/G or G/G genotype (T/T 6.7±0.3 vs T/G 8.9±0.4 or G/G 8.9±0.7, p =0.0009). A significant correlation of C‐peptide concentrations with blood glucose (BG) 60 min after glucose intake was only found in PW with the T/T genotype ( r =0.6, p <0.0004). Similarly, a significant correlation of insulin concentrations with BG 60 min after glucose intake was observed in PW with T/T genotype ( r =0.5, p <0.0001) and T/G genotype ( r =0.24, p <0.03) but not in PW with G/G genotype ( r =0.01, p =0.9). From our data we conclude that in PW with the alanine substitution in the NBF‐2 region, the insulin response of the pancreatic β‐cell after glucose intake is enhanced and does not correlate with actual BG levels