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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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                     name:The Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo
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                        name:The Institute for Diabetes Care and Research, Asahi Life Foundation, Tokyo, Japan
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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: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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