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

Sci Transl Med. 2017 Jun 14;9(394):eaah4477. doi: 10.1126/scitranslmed.aah4477.

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.

Trial registration: ClinicalTrials.gov NCT02801448.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Cell Line
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Glucose / metabolism*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Isothiocyanates / therapeutic use*
  • Liver / drug effects*
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism
  • Obesity / drug therapy
  • Obesity / metabolism

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • hemoglobin A1c protein, human
  • sulforafan
  • Glucose

Associated data

  • ClinicalTrials.gov/NCT02801448