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ARS Home » Plains Area » Houston, Texas » Children's Nutrition Research Center » Research » Publications at this Location » Publication #342810
Title: Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes

Author
item AXELSSON, ANNIKA - Lund University
item TUBBS, EMILY - Lund University
item MECHAM, BRIG - University Of Texas
item CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC)
item NENONEN, HANNAH - Lund University
item TANG, YUNZHAO - Lund University
item FAHEY, JED - Johns Hopkins University
item DERRY, JONATHAN - University Of Texas
item WOLLHEIM, CLAES - Lund University
item WIERUP, NILS - Lund University
item MOREY, HAYMOND - Children'S Nutrition Research Center (CNRC)
item FRIEND, STEPHEN - University Of Texas
item MULDER, HINDRIK - Lund University
item ROSENGREN, ANDERS - Lund University

Submitted to: Science Translational Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/5/2017
Publication Date: 6/14/2017
Citation: Axelsson, A.S., Tubbs, E., Mecham, B., Chacko, S., Nenonen, H.A., Tang, Y., Fahey, J.W., Derry, J.M., Wollheim, C.B., Wierup, N., Morey, H.W., Friend, S.H., Mulder, H., Rosengren, A.H. 2017. Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes. Science Translational Medicine. doi:10.1126/scitranslmed.aah4477.

Interpretive Summary: Diabetes is affecting a growing number of the population, with more than 300 million people worldwide having the disease and even more having pre-diabetes. Increased glucose production in liver has been reported in Type 2 diabetes (T2D). The objective of this research was to identify compounds to treat exaggerated hepatic glucose production in patients with T2D. This study demonstrated that a naturally occurring compound sulphoraphane found in cruciferous vegetable such as broccoli may have the potential to reverse the disease signature in liver tissue. Our findings indicate that Sulphoraphane suppressed glucose production and decreased the expression of key enzymes associated in the glucose synthesis from liver cells. Further, Sulforaphane provided as concentrated broccoli sprout extract, reduced fasting blood glucose and HbA1c in obese dysregulated patients with type 2 diabetes. This study shows that Sulphoraphane could provide additional treatment options to reduce exaggerated hepatic glucose production in T2D condition.

Technical 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.