PMID- 28615356
OWN - NLM
STAT- MEDLINE
DCOM- 20180319
LR  - 20221207
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Linking)
VI  - 9
IP  - 394
DP  - 2017 Jun 14
TI  - Sulforaphane reduces hepatic glucose production and improves glucose control in 
      patients with type 2 diabetes.
LID - eaah4477 [pii]
LID - 10.1126/scitranslmed.aah4477 [doi]
AB  - 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.
CI  - Copyright (c) 2017 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Axelsson, Annika S
AU  - Axelsson AS
AUID- ORCID: 0000-0002-5826-3159
AD  - Department of Clinical Sciences, Lund University Diabetes Center, Malmo, SE-20502 
      Malmo, Sweden.
FAU - Tubbs, Emily
AU  - Tubbs E
AUID- ORCID: 0000-0003-4925-9374
AD  - Department of Clinical Sciences, Lund University Diabetes Center, Malmo, SE-20502 
      Malmo, Sweden.
FAU - Mecham, Brig
AU  - Mecham B
AUID- ORCID: 0000-0002-4945-026X
AD  - Trialomics, Seattle, WA 98115, USA.
FAU - Chacko, Shaji
AU  - Chacko S
AUID- ORCID: 0000-0003-4283-1884
AD  - U.S. Department of Agriculture/Agricultural Research Service, Children's 
      Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 
      Houston, TX 77030, USA.
FAU - Nenonen, Hannah A
AU  - Nenonen HA
AUID- ORCID: 0000-0002-0287-9413
AD  - Department of Clinical Sciences, Lund University Diabetes Center, Malmo, SE-20502 
      Malmo, Sweden.
FAU - Tang, Yunzhao
AU  - Tang Y
AD  - Department of Clinical Sciences, Lund University Diabetes Center, Malmo, SE-20502 
      Malmo, Sweden.
FAU - Fahey, Jed W
AU  - Fahey JW
AUID- ORCID: 0000-0002-2129-1834
AD  - Departments of Medicine, Pharmacology and Molecular Sciences, and International 
      Health, and Cullman Chemoprotection Center, Johns Hopkins University, Baltimore, 
      MD 21205, USA.
FAU - Derry, Jonathan M J
AU  - Derry JMJ
AD  - Sage Bionetworks, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
FAU - Wollheim, Claes B
AU  - Wollheim CB
AUID- ORCID: 0000-0002-4570-9879
AD  - Department of Clinical Sciences, Lund University Diabetes Center, Malmo, SE-20502 
      Malmo, Sweden.
AD  - Department of Cell Physiology and Metabolism, University Medical Center, CH-1211 
      Geneva, Switzerland.
FAU - Wierup, Nils
AU  - Wierup N
AUID- ORCID: 0000-0001-6824-4093
AD  - Department of Clinical Sciences, Lund University Diabetes Center, Malmo, SE-20502 
      Malmo, Sweden.
FAU - Haymond, Morey W
AU  - Haymond MW
AUID- ORCID: 0000-0003-0631-2913
AD  - U.S. Department of Agriculture/Agricultural Research Service, Children's 
      Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, 
      Houston, TX 77030, USA.
FAU - Friend, Stephen H
AU  - Friend SH
AUID- ORCID: 0000-0002-0830-7600
AD  - Sage Bionetworks, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
FAU - Mulder, Hindrik
AU  - Mulder H
AD  - Department of Clinical Sciences, Lund University Diabetes Center, Malmo, SE-20502 
      Malmo, Sweden.
FAU - Rosengren, Anders H
AU  - Rosengren AH
AUID- ORCID: 0000-0002-9333-5736
AD  - Department of Clinical Sciences, Lund University Diabetes Center, Malmo, SE-20502 
      Malmo, Sweden. anders.rosengren@gu.se.
AD  - Sage Bionetworks, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
AD  - Institute of Neuroscience and Physiology, University of Gothenburg, SE-40530 
      Goteborg, Sweden.
LA  - eng
SI  - ClinicalTrials.gov/NCT02801448
PT  - Journal Article
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Isothiocyanates)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Sulfoxides)
RN  - 0 (hemoglobin A1c protein, human)
RN  - GA49J4310U (sulforaphane)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
CIN - Nat Rev Endocrinol. 2017 Aug;13(8):437. PMID: 28664922
MH  - Animals
MH  - Blood Glucose/drug effects
MH  - Cell Line
MH  - Diabetes Mellitus, Type 2/*drug therapy/*metabolism
MH  - Female
MH  - Glucose/*metabolism
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/therapeutic use
MH  - Isothiocyanates/*therapeutic use
MH  - Liver/*drug effects/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-E2-Related Factor 2/metabolism
MH  - Obesity/drug therapy/metabolism
MH  - Sulfoxides
EDAT- 2017/06/16 06:00
MHDA- 2018/03/20 06:00
CRDT- 2017/06/16 06:00
PHST- 2016/06/28 00:00 [received]
PHST- 2017/02/23 00:00 [revised]
PHST- 2017/05/05 00:00 [accepted]
PHST- 2017/06/16 06:00 [entrez]
PHST- 2017/06/16 06:00 [pubmed]
PHST- 2018/03/20 06:00 [medline]
AID - 9/394/eaah4477 [pii]
AID - 10.1126/scitranslmed.aah4477 [doi]
PST - ppublish
SO  - Sci Transl Med. 2017 Jun 14;9(394):eaah4477. doi: 10.1126/scitranslmed.aah4477.