Journal
SCIENCE TRANSLATIONAL MEDICINE
Volume 9, Issue 394, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aah4477
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Funding
- Ragnar Soderberg Foundation
- Swedish Foundation for Strategic Research
- Lantmannen Research Foundation
- NovoNordisk Foundation
- ALF Region Skane
- Hjelt Foundation
- Lewis B. and Dorothy Cullman Foundation
- Knut and Alice Wallenberg's foundation via the Wallenberg Centre for Molecular and Translational Medicine in Gothenburg
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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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