TY - JOUR

T1 - The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes

AU - Nielsen, Eva-Maria D

AU - Hansen, Lars

AU - Carstensen, Bendix

AU - Echwald, Søren Morgenthaler

AU - Drivsholm, Thomas

AU - Glümer, Charlotte

AU - Thorsteinsson, Birger

AU - Borch-Johnsen, Knut

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2003

Y1 - 2003

N2 - The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum insulin release. In a study comprising 519 unrelated glucose-tolerant subjects, we addressed the question as to whether the E23K variant was related to reduced serum insulin release during an oral glucose tolerance test (OGTT). Furthermore, the polymorphism was examined in a case-control study comprising 803 type 2 diabetic patients and 862 glucose-tolerant control subjects. The E23K variant was associated with significant reductions in the insulinogenic index (P = 0.022) and serum insulin levels under the response curve during an OGTT (0-120 min) (P = 0.014) as well as with an increase in BMI (P = 0.013). In the present study, the association of the E23K polymorphism with type 2 diabetes was not significant (P = 0.26). However, the K23K genotype significantly associated with type 2 diabetes in a meta-analysis of white case and control subjects (n = 2,824, odds ratio [OR] 1.49, P = 0.00022). In conclusion, the widespread E23K polymorphism may have a diabetogenic effect by impairing glucose-induced insulin release and increasing BMI.

AB - The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum insulin release. In a study comprising 519 unrelated glucose-tolerant subjects, we addressed the question as to whether the E23K variant was related to reduced serum insulin release during an oral glucose tolerance test (OGTT). Furthermore, the polymorphism was examined in a case-control study comprising 803 type 2 diabetic patients and 862 glucose-tolerant control subjects. The E23K variant was associated with significant reductions in the insulinogenic index (P = 0.022) and serum insulin levels under the response curve during an OGTT (0-120 min) (P = 0.014) as well as with an increase in BMI (P = 0.013). In the present study, the association of the E23K polymorphism with type 2 diabetes was not significant (P = 0.26). However, the K23K genotype significantly associated with type 2 diabetes in a meta-analysis of white case and control subjects (n = 2,824, odds ratio [OR] 1.49, P = 0.00022). In conclusion, the widespread E23K polymorphism may have a diabetogenic effect by impairing glucose-induced insulin release and increasing BMI.

KW - Amino Acid Substitution

KW - Blood Glucose

KW - Diabetes Mellitus, Type 2

KW - Genetic Variation

KW - Genotype

KW - Glucose Intolerance

KW - Glucose Tolerance Test

KW - Humans

KW - Insulin

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Potassium Channels, Inwardly Rectifying

KW - Risk Factors

M3 - Journal article

C2 - 12540638

VL - 52

SP - 573

EP - 577

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 2

ER -