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

1. Annika S. Axelsson1, 
2. Emily Tubbs1, 
3. Brig Mecham2, 
4. Shaji Chacko3, 
5. Hannah A. Nenonen1, 
6. Yunzhao Tang1, 
7. Jed W. Fahey4, 
8. Jonathan M. J. Derry5, 
9. Claes B. Wollheim1,6, 
10. Nils Wierup1, 
11. Morey W. Haymond3, 
12. Stephen H. Friend5, 
13. Hindrik Mulder1 and 
14. Anders H. Rosengren1,5,7,*

+ See all authors and affiliations

Science Translational Medicine  14 Jun 2017:
Vol. 9, Issue 394, eaah4477
DOI: 10.1126/scitranslmed.aah4477

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Another reason to eat your broccoli

Type 2 diabetes is becoming increasingly common worldwide, and not all patients can be successfully treated with the existing drugs. Axelsson et al. analyzed the pattern of gene expression associated with type 2 diabetes and compared it to the gene signatures for thousands of drug candidates to find compounds that could counteract the effects of diabetes. The leading candidate from this analysis was sulforaphane, a natural compound found in broccoli and other vegetables. The authors showed that sulforaphane inhibits glucose production in cultured cells and improves glucose tolerance in rodents on high-fat or high-fructose diets. Moreover, in a clinical trial, sulforaphane-containing broccoli sprout extract was well tolerated and improved fasting glucose in human patients with obesity and dysregulated 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.

• Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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