About the Authors

Hemang Parikh

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

Emma Carlsson

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

William A Chutkow

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

Lovisa E Johansson

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

Heidi Storgaard

Affiliation Steno Diabetes Center, Gentofte, Denmark

Pernille Poulsen

Affiliation Steno Diabetes Center, Gentofte, Denmark

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

Christine Ladd

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

P. Christian Schulze

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

Michael J Mazzini

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

Christine Bjørn Jensen

Affiliation Steno Diabetes Center, Gentofte, Denmark

Anna Krook

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

Marie Björnholm

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

Hans Tornqvist

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

Juleen R Zierath

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

Martin Ridderstråle

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

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

Richard T Lee

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

Allan Vaag

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

Leif C Groop

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

Vamsi K Mootha

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

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.