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Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes

Axelsson, Annika S. LU ; Tubbs, Emily LU ; Mecham, Brig; Chacko, Shaji; Nenonen, Hannah A. LU ; Tang, Yunzhao LU ; Fahey, Jed W.; Derry, Jonathan M.J.; Wollheim, Claes B. LU and Wierup, Nils LU , et al. (2017) In Science Translational Medicine 9(394).
Abstract

A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature. Sulforaphane suppressed glucose production from hepatic cells by nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and decreased expression of key enzymes in gluconeogenesis. Moreover, sulforaphane reversed... (More)

A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature. Sulforaphane suppressed glucose production from hepatic cells by nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and decreased expression of key enzymes in gluconeogenesis. Moreover, sulforaphane reversed the disease signature in the livers from diabetic animals and attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of metformin. Finally, sulforaphane, provided as concentrated broccoli sprout extract, reduced fasting blood glucose and glycated hemoglobin (HbA1c) in obese patients with dysregulated type 2 diabetes.

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published
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Science Translational Medicine
volume
9
issue
394
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85020922910
  • wos:000403204200001
ISSN
1946-6234
DOI
10.1126/scitranslmed.aah4477
language
English
LU publication?
yes
id
62c136f9-b7e0-443e-93a6-3c6a69153320
date added to LUP
2017-08-11 15:20:29
date last changed
2018-07-01 04:48:14
@article{62c136f9-b7e0-443e-93a6-3c6a69153320,
  abstract     = {<p>A potentially useful approach for drug discovery is to connect gene expression profiles of disease-affected tissues ("disease signatures") to drug signatures, but it remains to be shown whether it can be used to identify clinically relevant treatment options. We analyzed coexpression networks and genetic data to identify a disease signature for type 2 diabetes in liver tissue. By interrogating a library of 3800 drug signatures, we identified sulforaphane as a compound that may reverse the disease signature. Sulforaphane suppressed glucose production from hepatic cells by nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) and decreased expression of key enzymes in gluconeogenesis. Moreover, sulforaphane reversed the disease signature in the livers from diabetic animals and attenuated exaggerated glucose production and glucose intolerance by a magnitude similar to that of metformin. Finally, sulforaphane, provided as concentrated broccoli sprout extract, reduced fasting blood glucose and glycated hemoglobin (HbA1c) in obese patients with dysregulated type 2 diabetes.</p>},
  articleno    = {4477},
  author       = {Axelsson, Annika S. and Tubbs, Emily and Mecham, Brig and Chacko, Shaji and Nenonen, Hannah A. and Tang, Yunzhao and Fahey, Jed W. and Derry, Jonathan M.J. and Wollheim, Claes B. and Wierup, Nils and Haymond, Morey W and Friend, Stephen H. and Mulder, Hindrik and Rosengren, Anders H.},
  issn         = {1946-6234},
  language     = {eng},
  month        = {06},
  number       = {394},
  publisher    = {American Association for the Advancement of Science (AAAS)},
  series       = {Science Translational Medicine},
  title        = {Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes},
  url          = {http://dx.doi.org/10.1126/scitranslmed.aah4477},
  volume       = {9},
  year         = {2017},
}