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Topics {✒️}

single nucleotide polymorphisms transcriptional coactivator glut4 translocation-related genes association study type ii diabetes privacy choices/manage cookies type 2 diabetes nuclear receptor pparγ genetic variation diabetic subjects related subjects gly482ser polymorphism type ii european economic area asahi life foundation susceptibility gene conditions privacy policy confer insulin resistance insulin resistance index study suggested accepting optional cookies scope submit manuscript plasma fasting insulin newly detected snps pgc-1α activation diabetes mellitus diabetes care journal finder publish search search article cite kadowaki crest article hara information privacy policy personal data books a pgc-1 gene susceptibility insulin resistance optional cookies manage preferences fasting insulin hiroshima research data protection essential cookies cookies skip insulin sensitivity insulin-dependent journal publish

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• PGC-1α activation: a therapeutic target for type 2 diabetes?

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WebPage:
      mainEntity:
         headline:A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes
         description: Aims/hypothesis. Peroxisome proliferator activated receptor γ coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARγ, plays a role in adaptive thermogenesis and insulin sensitivity. Plasma fasting insulin has been linked to the chromosomal region where the PGC-1 gene is located. Thus, PGC-1 can be viewed as a functional and positional candidate for the susceptibility gene for Type II (non-insulin-dependent) diabetes mellitus. Methods. After screening the PGC-1 gene for single nucleotide polymorphisms (SNPs), we performed an association study using the newly detected SNPs in 537 Type II diabetic patients and 417 non-diabetic subjects. Results. We found three relatively frequent SNPs in the PGC-1 gene (IVS4-11T > C, Thr394Thr and Gly482Ser). There were significant differences in fasting insulin (Gly/Gly; 37.7 ± 1.43, Gly/Ser; 40.2 ± 1.21, Ser/Ser; 44.3 ± 1.82 pmol/l, p = 0.018) and insulin resistance index (Gly/Gly; 1.48 ± 0.06, Gly/Ser; 1.56 ± 0.05, Ser/Ser; 1.75 ± 0.08, p = 0.027) according to the genotype of the Gly482Ser polymorphism. The Thr394Thr – Gly482Ser haplotype was associated with Type II diabetes (p = 0.00003). Conclusion/interpretation. The results of this study suggested that the PGC-1 gene might be implicated in the pathogenesis of Type II diabetes.
         datePublished:2002-04-23T00:00:00Z
         dateModified:2002-04-23T00:00:00Z
         pageStart:740
         pageEnd:743
         sameAs:https://doi.org/10.1007/s00125-002-0803-z
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            Single nucleotide polymorphism HOMA transcriptional coactivator susceptibility gene association study direct sequencing linkage disequilibrium haplotype PCR-RFLP
            Internal Medicine
            Metabolic Diseases
            Human Physiology
         image:
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                     name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655
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                        name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
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                        name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
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               affiliation:
                     name:The Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo
                     address:
                        name:The Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo, Japan
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               name:Y. Akanuma
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                     name:CREST, Japan Science and Technology Corporation (JST), Chuo-ku, Tokyo
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                        name:CREST, Japan Science and Technology Corporation (JST), Chuo-ku, Tokyo, Japan
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               name:C. Ito
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                        name:Hiroshima Atomic Bomb Casualty Council Health Management Center, Hiroshima, Japan
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                        name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
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                        name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
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      headline:A genetic variation in the PGC-1 gene could confer insulin resistance and susceptibility to Type II diabetes
      description: Aims/hypothesis. Peroxisome proliferator activated receptor γ coactivator-1 (PGC-1), a transcriptional coactivator of the nuclear receptor PPARγ, plays a role in adaptive thermogenesis and insulin sensitivity. Plasma fasting insulin has been linked to the chromosomal region where the PGC-1 gene is located. Thus, PGC-1 can be viewed as a functional and positional candidate for the susceptibility gene for Type II (non-insulin-dependent) diabetes mellitus. Methods. After screening the PGC-1 gene for single nucleotide polymorphisms (SNPs), we performed an association study using the newly detected SNPs in 537 Type II diabetic patients and 417 non-diabetic subjects. Results. We found three relatively frequent SNPs in the PGC-1 gene (IVS4-11T > C, Thr394Thr and Gly482Ser). There were significant differences in fasting insulin (Gly/Gly; 37.7 ± 1.43, Gly/Ser; 40.2 ± 1.21, Ser/Ser; 44.3 ± 1.82 pmol/l, p = 0.018) and insulin resistance index (Gly/Gly; 1.48 ± 0.06, Gly/Ser; 1.56 ± 0.05, Ser/Ser; 1.75 ± 0.08, p = 0.027) according to the genotype of the Gly482Ser polymorphism. The Thr394Thr – Gly482Ser haplotype was associated with Type II diabetes (p = 0.00003). Conclusion/interpretation. The results of this study suggested that the PGC-1 gene might be implicated in the pathogenesis of Type II diabetes.
      datePublished:2002-04-23T00:00:00Z
      dateModified:2002-04-23T00:00:00Z
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         Single nucleotide polymorphism HOMA transcriptional coactivator susceptibility gene association study direct sequencing linkage disequilibrium haplotype PCR-RFLP
         Internal Medicine
         Metabolic Diseases
         Human Physiology
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      name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
      name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
      name:The Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo, Japan
      name:CREST, Japan Science and Technology Corporation (JST), Chuo-ku, Tokyo, Japan
      name:Hiroshima Atomic Bomb Casualty Council Health Management Center, Hiroshima, Japan
      name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan
      name:Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan

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