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Emma A Nilsson

Assistant researcher

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TXNIP regulates peripheral glucose metabolism in humans

Author

  • Hemang Parikh
  • Emma A Nilsson
  • William A. Chutkow
  • Lovisa Johansson
  • Heidi Storgaard
  • Pernille Poulsen
  • Richa Saxena
  • Christine Ladd
  • P. Christian Schulze
  • Michael J. Mazzini
  • Christine Bjorn Jensen
  • Anna Krook
  • Marie Bjornholm
  • Hans Tornqvist
  • Juleen R. Zierath
  • Martin Ridderstråle
  • David Altshuler
  • Richard T. Lee
  • Allan Vaag
  • Leif Groop
  • Vamsi K. Mootha

Summary, in English

Background Type 2 diabetes mellitus ( T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure. Methods and Findings We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein ( TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. Conclusions TXNIP regulates both insulin-dependent and insulin- independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Department of Clinical Sciences, Malmö

Publishing year

2007

Language

English

Pages

868-879

Publication/Series

PLoS Medicine

Volume

4

Issue

5

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1549-1676