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

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.

Details

Authors
Organisations
External organisations
  • Trialomics
  • Baylor College of Medicine
  • Johns Hopkins University
  • Sage Bionetworks
  • University of Geneva Medical School
  • University of Gothenburg
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Article number4477
JournalScience Translational Medicine
Volume9
Issue number394
Publication statusPublished - 2017 Jun 14
Publication categoryResearch
Peer-reviewedYes