Format

Send to

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

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

Author information

1
Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden.
2
Trialomics, Seattle, WA 98115, USA.
3
U.S. Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
4
Departments of Medicine, Pharmacology and Molecular Sciences, and International Health, and Cullman Chemoprotection Center, Johns Hopkins University, Baltimore, MD 21205, USA.
5
Sage Bionetworks, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
6
Department of Cell Physiology and Metabolism, University Medical Center, CH-1211 Geneva, Switzerland.
7
Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden. anders.rosengren@gu.se.
8
Institute of Neuroscience and Physiology, University of Gothenburg, SE-40530 Göteborg, Sweden.

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.

PMID:
28615356
DOI:
10.1126/scitranslmed.aah4477
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center