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Research Article

TXNIP Regulates Peripheral Glucose Metabolism in Humans

  • Hemang Parikh,

    Affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden

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  • Emma Carlsson,

    Affiliations: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden, Steno Diabetes Center, Gentofte, Denmark

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  • William A Chutkow,

    Affiliation: Cardiovascular Division, Brigham and Women's Hospital, Cambridge, Massachusetts, United States of America

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  • Lovisa E Johansson,

    Affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden

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  • Heidi Storgaard,

    Affiliation: Steno Diabetes Center, Gentofte, Denmark

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  • Pernille Poulsen,

    Affiliation: Steno Diabetes Center, Gentofte, Denmark

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  • Richa Saxena,

    Affiliations: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Christine Ladd,

    Affiliation: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America

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  • P. Christian Schulze,

    Affiliation: Cardiovascular Division, Brigham and Women's Hospital, Cambridge, Massachusetts, United States of America

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  • Michael J Mazzini,

    Affiliation: Cardiovascular Division, Brigham and Women's Hospital, Cambridge, Massachusetts, United States of America

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  • Christine Bjørn Jensen,

    Affiliation: Steno Diabetes Center, Gentofte, Denmark

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  • Anna Krook,

    Affiliation: Department of Physiology and Pharmacology, Section Integrative Physiology, Karolinska Institute, Stockholm, Sweden

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  • Marie Björnholm,

    Affiliation: Department of Molecular Medicine and Surgical Sciences, Section Integrative Physiology, Karolinska Institutet, Stockholm, Sweden

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  • Hans Tornqvist,

    Affiliation: Diabetes Biology, Novo Nordisk A/S, Maaloev, Denmark

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  • Juleen R Zierath,

    Affiliation: Department of Molecular Medicine and Surgical Sciences, Section Integrative Physiology, Karolinska Institutet, Stockholm, Sweden

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  • Martin Ridderstråle,

    Affiliation: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden

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  • David Altshuler,

    Affiliations: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Richard T Lee,

    Affiliation: Cardiovascular Division, Brigham and Women's Hospital, Cambridge, Massachusetts, United States of America

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  • Allan Vaag,

    Affiliations: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden, Steno Diabetes Center, Gentofte, Denmark

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  • Leif C Groop mail,

    To whom correspondence should be addressed. E-mail: Leif.Groop@med.lu.se (LCG); vamsi@hms.harvard.edu (VKM)

    Affiliations: Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden, Program in Molecular Medicine, Helsinki University, Helsinki, Finland

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  • Vamsi K Mootha mail

    To whom correspondence should be addressed. E-mail: Leif.Groop@med.lu.se (LCG); vamsi@hms.harvard.edu (VKM)

    Affiliations: Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America, Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America

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  • Published: May 01, 2007
  • DOI: 10.1371/journal.pmed.0040158

About the Authors

Hemang Parikh, Emma Carlsson, Lovisa E Johansson, Martin Ridderstråle, Allan Vaag, Leif C Groop
Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden
Emma Carlsson, Heidi Storgaard, Pernille Poulsen, Christine Bjørn Jensen, Allan Vaag
Steno Diabetes Center, Gentofte, Denmark
William A Chutkow, P. Christian Schulze, Michael J Mazzini, Richard T Lee
Cardiovascular Division, Brigham and Women's Hospital, Cambridge, Massachusetts, United States of America
Richa Saxena, Christine Ladd, David Altshuler, Vamsi K Mootha
Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America
Richa Saxena, David Altshuler, Vamsi K Mootha
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America
Richa Saxena, David Altshuler
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
Anna Krook
Department of Physiology and Pharmacology, Section Integrative Physiology, Karolinska Institute, Stockholm, Sweden
Marie Björnholm, Juleen R Zierath
Department of Molecular Medicine and Surgical Sciences, Section Integrative Physiology, Karolinska Institutet, Stockholm, Sweden
Hans Tornqvist
Diabetes Biology, Novo Nordisk A/S, Maaloev, Denmark
Leif C Groop
Program in Molecular Medicine, Helsinki University, Helsinki, Finland
Vamsi K Mootha
Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America

Corresponding Authors

Competing Interests

HT is employed at Novo Nordisk A/S, Denmark and owns a minor amount of employers stock in this Company. LCG is a member of the editorial board of PLoS Medicine.

Author Contributions

HP analysed the microarray data, performed the GEE analysis, carried out the resequencing of TXNIP, and drafted the manuscript. EC, LEJ, and MR studied the effects of glucose and insulin on TXNIP expression in the human adipocyte cell line and carried out the real-time PCR studies of TXNIP, G0S2, and BCL6. WAC, PCS, MJM, and RTL performed the glucose uptake studies in 3T3-L1 cells following genetic manipulation of Txnip expression. HS, PP, CBJ, and AV were responsible for the clinical and metabolic studies including the hyperinsulinemic euglycemic clamp studies. RS and DA were responsible for the genetic association studies. CL performed the microarray experiments. AK, MB, and JRZ performed glucose uptake studies in human skeletal muscle cells following siRNA of TXNIP. HT provided the human adipocyte cell line and was involved in planning the experiments studying the effect of glucose and insulin on TXNIP expression in these cells. LCG and VKM conceived the project, designed the study, and jointly supervised all phases of the study as well as the drafting of the manuscript.