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

Annika S. Axelsson, Emily Tubbs, Brig Mecham, Shaji Chacko, Hannah A. Nenonen, Yunzhao Tang, Jed W Fahey, Jonathan M.J. Derry, Claes B. Wollheim, Nils Wierup, Morey W. Haymond, Stephen H. Friend, Hindrik Mulder, Anders H. Rosengren

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Article number4477
JournalScience Translational Medicine
Volume9
Issue number394
DOIs
StatePublished - Jun 14 2017

Fingerprint

Type 2 Diabetes Mellitus
Glucose
Liver
Glucose Intolerance
Gluconeogenesis
Metformin
Brassica
Glycosylated Hemoglobin A
Drug Discovery
Transcriptome
Pharmaceutical Preparations
Blood Glucose
Hepatocytes
Fasting
sulforafan
Enzymes
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Axelsson, A. S., Tubbs, E., Mecham, B., Chacko, S., Nenonen, H. A., Tang, Y., ... Rosengren, A. H. (2017). Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Science Translational Medicine, 9(394), [4477]. https://doi.org/10.1126/scitranslmed.aah4477

Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. / Axelsson, Annika S.; Tubbs, Emily; Mecham, Brig; Chacko, Shaji; Nenonen, Hannah A.; Tang, Yunzhao; Fahey, Jed W; Derry, Jonathan M.J.; Wollheim, Claes B.; Wierup, Nils; Haymond, Morey W.; Friend, Stephen H.; Mulder, Hindrik; Rosengren, Anders H.

In: Science Translational Medicine, Vol. 9, No. 394, 4477, 14.06.2017.

Research output: Contribution to journalArticle

Axelsson, AS, Tubbs, E, Mecham, B, Chacko, S, Nenonen, HA, Tang, Y, Fahey, JW, Derry, JMJ, Wollheim, CB, Wierup, N, Haymond, MW, Friend, SH, Mulder, H & Rosengren, AH 2017, 'Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes', Science Translational Medicine, vol. 9, no. 394, 4477. https://doi.org/10.1126/scitranslmed.aah4477
Axelsson, Annika S. ; Tubbs, Emily ; Mecham, Brig ; Chacko, Shaji ; Nenonen, Hannah A. ; Tang, Yunzhao ; Fahey, Jed W ; Derry, Jonathan M.J. ; Wollheim, Claes B. ; Wierup, Nils ; Haymond, Morey W. ; Friend, Stephen H. ; Mulder, Hindrik ; Rosengren, Anders H. / Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. In: Science Translational Medicine. 2017 ; Vol. 9, No. 394.
@article{918d9b25f9ea46ae8fc16c2de24188df,
title = "Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes",
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 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.",
author = "Axelsson, {Annika S.} and Emily Tubbs and Brig Mecham and Shaji Chacko and Nenonen, {Hannah A.} and Yunzhao Tang and Fahey, {Jed W} and Derry, {Jonathan M.J.} and Wollheim, {Claes B.} and Nils Wierup and Haymond, {Morey W.} and Friend, {Stephen H.} and Hindrik Mulder and Rosengren, {Anders H.}",
year = "2017",
month = "6",
day = "14",
doi = "10.1126/scitranslmed.aah4477",
language = "English (US)",
volume = "9",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "394",

}

TY - JOUR

T1 - Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes

AU - Axelsson, Annika S.

AU - Tubbs, Emily

AU - Mecham, Brig

AU - Chacko, Shaji

AU - Nenonen, Hannah A.

AU - Tang, Yunzhao

AU - Fahey, Jed W

AU - Derry, Jonathan M.J.

AU - Wollheim, Claes B.

AU - Wierup, Nils

AU - Haymond, Morey W.

AU - Friend, Stephen H.

AU - Mulder, Hindrik

AU - Rosengren, Anders H.

PY - 2017/6/14

Y1 - 2017/6/14

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85020922910&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020922910&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aah4477

DO - 10.1126/scitranslmed.aah4477

M3 - Article

C2 - 28615356

AN - SCOPUS:85020922910

VL - 9

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 394

M1 - 4477

ER -