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Genetic variations in the pancreatic ATP-sensitive potassium channel, β-cell dysfunction, and susceptibility to type 2 diabetes

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Abstract

The KCNJ11 and ABCC8 genes encode the components of the pancreatic ATP-sensitive potassium (KATP) channel, which regulates insulin secretion by β-cells and hence could be involved in the pathogenesis of type 2 diabetes (T2D). The KCNJ11 E23K and ABCC8 exon 31 variants have been studied in 127 Russian T2D patients and 117 controls using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The KCNJ11 E23 variant and the ABCC8 exon 31 allele A were associated with higher risk of T2D [Odds ratio (OR) of 1.53 (P = 0.023) and 2.41 (P = 1.95 × 10−5)], respectively. Diabetic carriers of the ABCC8 G/G variant had reduced 2 h glucose compared to A/A + A/G (P = 0.031). The G/G genotype of ABCC8 was also significantly associated with increased both fasting and 2 h serum insulin in diabetic and non-diabetic patients. A HOMA-β value characterizing the β-cell homeostasis was higher in the non-diabetic carriers homozygous for G/G (98.0 ± 46.9) then for other genotypes (HOMA-β = 85.6 ± 45.5 for A/A + A/G, P = 0.0015). The KCNJ11 E23K and ABCC8 exon 31 variants contribute to susceptibility to T2D diabetes, glucose intolerance and altered insulin secretion in a Russian population.

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Authors and Affiliations

  1. Department of Pathology, University of Pittsburgh, A709 Scaife Hall, 3550 Terrace St, Pittsburgh, PA, 15261, USA

    D. A. Chistiakov

  2. Department of Molecular Diagnostics, National Research Center GosNIIgenetika, Moscow, Russia

    D. A. Chistiakov, V. A. Potapov, D. C. Khodirev & V. V. Nosikov

  3. Institute of Diabetes, Endocrinological Research Center, Moscow, Russia

    M. S. Shamkhalova & M. V. Shestakova

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  1. D. A. Chistiakov
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  2. V. A. Potapov
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  3. D. C. Khodirev
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  4. M. S. Shamkhalova
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  5. M. V. Shestakova
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  6. V. V. Nosikov
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Correspondence to D. A. Chistiakov.

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Chistiakov, D.A., Potapov, V.A., Khodirev, D.C. et al. Genetic variations in the pancreatic ATP-sensitive potassium channel, β-cell dysfunction, and susceptibility to type 2 diabetes. Acta Diabetol 46, 43–49 (2009). https://doi.org/10.1007/s00592-008-0056-5

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  • DOI: https://doi.org/10.1007/s00592-008-0056-5

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