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  • 1
    Electronic Resource
    Electronic Resource
    Variants in the sulphonylurea receptor gene: association of the exon 16–3t variant with Type II diabetes mellitus in Dutch Caucasians (1999)
    Springer
    Diabetologia 42 (1999), S. 617-620 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type II diabetes ; diabetes ; genetics ; sulphonylurea receptor ; prevalence.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. We have analysed to what extent two previously reported single nucleotide polymorphisms in the sulphonylurea receptor gene (SUR1) are associated with Type II (non-insulin-dependent) diabetes mellitus in The Netherlands. Furthermore, we estimated haplotype frequencies in control and diabetic populations, including data extracted from three other studies. Methods. Subjects with Type II diabetes (n = 388) and normoglycaemic subjects (n = 336) were randomly selected from two population-based studies, the Hoorn and Rotterdam studies. DNA was typed for variants in exon 16 (-3c→t variant in the splice acceptor site) and exon 18 (Thr759Thr, ACC→ACT). Results. The genotype frequencies in both populations were similar. We observed an association of the exon 16–3t variant with Type II diabetes (allele frequencies 0.41 % vs 0.48 % in NGT and Type II diabetes, respectively, p = 0.01). There was no association between Type II diabetes and the variant in exon 18 or the combination of both variants (p 〉 0.5). A strong linkage disequilibrium between the exon 16 and exon 18 variants was observed in the diabetic groups but not, or less pronounced, in the control groups from the different studies. Haplotype estimation shows that several different risk haplotypes exist in different Caucasian populations. Conclusion/interpretation. The exon 16–3t allele of the SUR1 gene is associated with Type II diabetes in the Netherlands. Based on estimated haplotype frequencies in different Caucasian populations we conclude that multiple haplotypes on the SUR1 gene seem to confer a risk for developing Type II diabetes in Caucasians. [Diabetologia (1999) 42: 617–620]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051203
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  • 2
    Electronic Resource
    Electronic Resource
    Hyperproinsulinaemia in impaired glucose tolerance is associated with a delayed insulin response to glucose (1999)
    Springer
    Diabetologia 42 (1999), S. 177-180 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Impaired glucose tolerance ; insulin ; proinsulin ; hyperglycaemic clamp ; beta-cell function ; insulin sensitivity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In subjects with impaired glucose tolerance hyperproinsulinaemia has been shown to be predictive for progression to Type II (non-insulin-dependent) diabetes mellitus. These findings are often interpreted as early indicators of an impaired beta-cell function. The aim of our study was to assess the potential determinants of hyperproinsulinaemia in subjects with impaired glucose tolerance. The study group consisted of 110 subjects, 45–74 years of age with mean 2 h plasma glucose concentrations between 8.6 and 11.1 mmol/l following two oral glucose tolerance tests. Subsequently, the hyperglycaemic clamp technique (10 mmol/l, with a priming infusion of 20 % glucose solution, 150 mg/kg) was used to assess the beta-cell function (time needed to reach the insulin peak) and insulin sensitivity (M/I value: glucose metabolised divided by insulin response, 150–180 min). Results showed that the intact-proinsulin:insulin ratio increased with increasing time needed to reach the insulin peak (0.065, 0.079 and 0.101; time needed to reach the insulin peak ≤ 5 min, 5 to 15 min, 〉 15 min; p 〈 0.05). The split-proinsulin:insulin ratio showed a similar association with the time needed to reach the insulin peak. These associations were independent of age, sex, body mass index and waist:hip ratio. In conclusion, this study shows that relative hyperproinsulinaemia is associated with an impaired beta-cell function in a study group of subjects with impaired glucose tolerance selected after two oral glucose tolerance tests. [Diabetologia (1999) 42: 177–180]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051136
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  • 3
    Electronic Resource
    Electronic Resource
    Reduced second phase insulin secretion in carriers of a sulphonylurea receptor gene variant associating with Type II diabetes mellitus (2000)
    Springer
    Diabetologia 43 (2000), S. 515-519 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type II diabetes mellitus, sulphonylurea receptor, genetics, insulin, beta cell, insulin secretion, impaired glucose tolerance, hyperglycaemic clamp.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The sulphonylurea receptor is a subunit of the ATP-sensitive potassium channel in the pancreatic beta cell. Mutations at nt –3 of the splice acceptor site of exon 16 and a silent mutation in exon 18 of the gene for the sulphonylurea receptor (SUR1) associate with Type II (non-insulin-dependent) diabetes mellitus in several independent populations. We investigated whether these gene variants associate with changes in the pattern of glucose-stimulated insulin secretion.¶Methods. Subjects who had normal glucose tolerance (n = 67) and subjects with an impaired glucose tolerance (n = 94), originating from two independent studies, were included in the study. Beta-cell function and insulin sensitivity were assessed by the hyperglycaemic clamp.¶Results. Frequencies of the exon 16 –3t allele in the normal and impaired glucose tolerant groups were 46 % and 44 % respectively (p = NS). The more rare exon 18 T allele showed frequencies of 5 and 7 % respectively (p = NS). We observed an approximately 25 % reduced second-phase insulin secretion in carriers of the exon 16 –3t allele in both groups (p 〈 0.05). Estimates of insulin sensitivity did not show differences between carriers and non-carriers. The variant in exon 18 and the combined presence of variants in exon 16 and exon 18 were not associated with differences in insulin secretion or insulin sensitivity in our study groups.¶Conclusion/interpretation. The diabetes associated exon 16 –3t variant of the SUR1 gene associates with a functional change of the beta cell as reflected by reduced second-phase insulin secretion in response to a standardized hyperglycaemia in normal and impaired glucose tolerant subjects. [Diabetologia (2000) 43: 515–519]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051337
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    Paper (German National Licenses)
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