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  • 1
    ISSN: 1432-0428
    Schlagwort(e): Non-insulin-dependent diabetes mellitus ; insulin resistance ; skeletal muscle glycogen synthase gene ; association ; Pima Indians
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Skeletal muscle glycogen synthase (encoded by GYS1 on chromosome 19ql3.3) is the rate-limiting enzyme in insulin-mediated non-oxidative glucose disposal. Our previous studies have demonstrated an impairment of insulin-stimulated GYS1 activities in insulin-resistant Pima Indians, and associations of non-insulin-dependent diabetes mellitus (NIDDM) with the GYS1 locus were reported recently in Finnish and Japanese populations. We have performed linkage and association analyses of GYS1 and seven additional DNA markers on 19q with NIDDM, and with parameters of insulin action in the Pima Indians. We have found a significant association of NIDDM with GYS1 genotypes (p=0.009), and with common GYS1 alleles (p=0.022) in the Pima Indians. We have performed a detailed comparative analysis of the GYS1 gene, mRNA, and protein product in insulin-sensitive and insulin-resistant Pima Indians. No mutations in GYS1 coding sequences were detected; nor did we find alterations of GYS1 mRNA expression or of its basal enzymatic activity in insulin-resistant Pima Indians. These results contrasted with a 25% reduction of immunoreactive protein in insulin-resistant subjects as detected by Western blotting with an antibody specific for the C-terminal end of GYS1 (t-test p=0.024; Wilcoxon's rank-sum test, p=0.04). Because no mutations were detected in the DNA encoding this epitope, the difference in immunoreactivity may reflect post-translational modification(s) of the protein rather than a difference in the gene itself, or it could have occurred by chance. We conclude that our data do not indicate alterations in the GYS1 gene as the cause for the observed association, and that a different locus near GYS1 may be the contributing genetic element.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): Keywords Non-insulin-dependent diabetes mellitus ; insulin resistance ; skeletal muscle glycogen synthase gene ; association ; Pima Indians.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Skeletal muscle glycogen synthase (encoded by GYS1 on chromosome 19q13.3) is the rate-limiting enzyme in insulin-mediated non-oxidative glucose disposal. Our previous studies have demonstrated an impairment of insulin-stimulated GYS1 activities in insulin-resistant Pima Indians, and associations of non-insulin-dependent diabetes mellitus (NIDDM) with the GYS1 locus were reported recently in Finnish and Japanese populations. We have performed linkage and association analyses of GYS1 and seven additional DNA markers on 19q with NIDDM, and with parameters of insulin action in the Pima Indians. We have found a significant association of NIDDM with GYS1 genotypes (p = 0.009), and with common GYS1 alleles (p = 0.022) in the Pima Indians. We have performed a detailed comparative analysis of the GYS1 gene, mRNA, and protein product in insulin-sensitive and insulin-resistant Pima Indians. No mutations in GYS1 coding sequences were detected; nor did we find alterations of GYS1 mRNA expression or of its basal enzymatic activity in insulin-resistant Pima Indians. These results contrasted with a 25 % reduction of immunoreactive protein in insulin-resistant subjects as detected by Western blotting with an antibody specific for the C-terminal end of GYS1 (t -test p = 0.024; Wilcoxon's rank-sum test, p = 0.04). Because no mutations were detected in the DNA encoding this epitope, the difference in immunoreactivity may reflect post-translational modification(s) of the protein rather than a difference in the gene itself, or it could have occurred by chance. We conclude that our data do not indicate alterations in the GYS1 gene as the cause for the observed association, and that a different locus near GYS1 may be the contributing genetic element. [Diabetologia (1996) 39: 314–321]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1573-4927
    Schlagwort(e): Mouse gene localization ; recombinant inbred lines ; mouse Chinese hamster somatic cell hybrids ; vitamin B12 binder
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Chemie und Pharmazie
    Notizen: Abstract Somatic cell hybrids, recombinant inbred (RI) mouse strains, and backcross breeding experiments were used to locate the gene of transcobalamin II (Tcn-2), the vitamin B12 binding protein in mouse serum. TCN-2 was found to be a useful genetic marker in the somatic cell hybrids. Selected hybrid clones were derived from fusions between GR mouse cells and the Chinese hamster cell line E36. Analysis of mouse specific chromosomal enzyme markers in relationship to TCN-2 secretion, in the hybrid clones, provided provisional evidence for assignment of the Tcn-2 locus to chromosome 11. The strain distribution pattern of the TCN-2 variants S and F in the RI series CXS, constructed from the cross of BALB/cHeA (TCN-2S) with STS/A (TCN-2F), implied a close linkage with the hemoglobin alpha-chain locus (Hba) on chromosome 11. Backcross breeding using inbred strains confirmed these findings and located the Tcn-2 gene closest to the centromere, linked with waved 2 (wa-2) and Hba with recombination frequencies of 6.9 and 19.2% each. The linkage group Tcn-2/wa-2/Hba was established.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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