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Epidemiological data collected over the last few decades have demonstrated the significant role of acute (especially postprandial) hyperglycaemia in the development of macrovascular complications in patients with type 2 diabetes. However, the influence of SUR1 exon 16-3c/t polymorphism on impaired insulin secretion during acute hyperglycaemic episodes has not yet been evaluated. We studied 40 type 2 diabetic patients. Single nucleotide polymorphism in the sulfonylurea receptor gene was examined by means of PCR-RLFP. In every patient, fasting insulin, proinsulin, C-peptide and 1,5-anhydro-d-glucitol concentrations were assayed as markers of insulin secretion, peripheral resistance to insulin, and acute hyperglycaemia. The distribution of SUR1 exon 16-3c/t polymorphism was tt 35%, tc -40%, and cc -25%. By means of analysis of covariance, it was revealed that 1,5-anhydro-d-glucitol plasma levels are associated with SUR1 exon 16-3c/t polymorphism. However, the HOMA(IR) score influenced 1,5-anhydro-d-glucitol levels in plasma at a higher level of statistical power than the genetic variant. Our results suggest that SUR1 exon 16-3c/t polymorphism is only a partial determinant of acute hyperglycaemia-cardiovascular risk factor in type 2 diabetes.

To assess the association of polymorphisms at the sulphonylurea receptor (SUR1) gene with the development of Type 2 diabetes mellitus, 456 subjects, 236 with Type 2 diabetes and 220 non-diabetic controls, were analysed for variants at exon 7, exon 22 and intron 24 of the SUR1 gene by the polymerase chain reaction and restriction fragment length polymorphism. The T761T substitution in exon 22 of the SUR1 gene was not found in either diabetic patients or non-diabetic controls. Both the exon 7 variant and the intron 24 variant were present in both groups at similar frequencies. No significant association was seen between either variant and obesity. Diabetic patients homozygous for the -3C allele of intron 24 had a higher ratio of positive family history than patients homozygous for the -3T allele (p = 0.03). We conclude that these polymorphisms are not major determinants of diabetes and obesity in the Japanese population.

1. Membrane currents were studied in single human blood eosinophils using the whole cell voltage clamp technique. The whole cell current-voltage relationship exhibited rectification about the membrane potential which followed the potassium equilibrium potential when [K+]o was raised. Elevation of [K+]o considerably potentiated inward current amplitude, and in some cells channel activity was discernible in the whole cell membrane current recordings. The single channel conductance was 24 +/- 1 pS ([K+]o, 100 mM; [K+]i, 140 mM), and eosinophils were found to have as few as three, and on average twenty, inward rectifier channels each. 2. The inward current was inhibited in a voltage-dependent manner by extracellular cations in order of potency Ba2+ > Cs+ > Na+. Intracellular acidification inhibited while alkalization augmented the inward current. Mg2+ contributed to rectification as dialysis with nominally Mg(2+)-free pipette solution was associated with an increase in the outward current during membrane polarization. 3. By reverse transcription-polymerase chain reaction (RT-PCR) using suitable primers on human eosinophils mRNA, an inward rectifier channel, Kir2.1, was identified, which is known from expression studies to have very similar properties to those found in this study. 4. Superoxide anion production or its stimulation by phorbol 12-myristate 13-acetate (PMA) was not significantly affected by depolarization with 140 mM [K+]o, or by 1 mM BaCl2. 5. It is concluded that the single channel currents and the whole cell current rectification observed in human blood eosinophils resulted from the presence of an inwardly rectifying potassium channel, probably Kir2.1.