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

Autor:	Axelsson AS; Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden., Tubbs E; Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden., Mecham B; Trialomics, Seattle, WA 98115, USA., Chacko S; U.S. Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Nenonen HA; Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden., Tang Y; Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden., Fahey JW; Departments of Medicine, Pharmacology and Molecular Sciences, and International Health, and Cullman Chemoprotection Center, Johns Hopkins University, Baltimore, MD 21205, USA., Derry JMJ; Sage Bionetworks, 1100 Fairview Avenue North, Seattle, WA 98109, USA., Wollheim CB; Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden.; Department of Cell Physiology and Metabolism, University Medical Center, CH-1211 Geneva, Switzerland., Wierup N; Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden., Haymond MW; U.S. Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA., Friend SH; Sage Bionetworks, 1100 Fairview Avenue North, Seattle, WA 98109, USA., Mulder H; Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden., Rosengren AH; Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden. anders.rosengren@gu.se.; Sage Bionetworks, 1100 Fairview Avenue North, Seattle, WA 98109, USA.; Institute of Neuroscience and Physiology, University of Gothenburg, SE-40530 Göteborg, Sweden.
Jazyk:	angličtina
Zdroj:	Science translational medicine [Sci Transl Med] 2017 Jun 14; Vol. 9 (394).
DOI:	10.1126/scitranslmed.aah4477
Abstrakt:	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. (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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