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 journalArticlepeer-review

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

ASJC Scopus subject areas

  • Medicine(all)

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