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

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.

Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach

“…In a more recent study, SFN administered as concentrated broccoli sprout extract suppressed glucose production from Systems Medicine Approach to NRF2 in Chronic Diseases Systems Medicine Approach to NRF2 in Chronic Diseases hepatocytes by nuclear translocation of NRF2 and decreased expression of key enzymes involved in gluconeogenesis. Moreover, SFN reduced fasting blood glucose and glycated hemoglobin in obese patients with T2DM (Axelsson et al, 2017). SFN-induced activation of NRF2 protected renal cells against lupus nephritis by reducing the ROS burden and by inhibiting the NF-kB and TGF-b1 signaling pathways (Jiang et al, 2014a).…”

“…6, it provides therapeutic benefit to the NRF2 subcluster of pathophenotypes related to glucose metabolism. In fact, SFN reduces hepatic glucose production and improves glucose control in patients with T2DM (Axelsson et al, 2017). Interestingly, some evidence suggests that metformin may be effective in preventing other nonglycemic pathophenotypes of the NRF2 diseasome, including cardiovascular (Nesti and Natali, 2017), respiratory (Sato et al, 2016), digestive (Bauer and Duca, 2016), neurodegenerative (Markowicz-Piasecka et al, 2017), autoimmune (Schuiveling et al, 2017), and neoplastic (Heckman-Stoddard et al, 2017) disorders.…”

In vitro Antidiabetic Activity of Sulforaphane

“…9,10 The total assay mixture composed of 1400 μl of 0.05 M sodium phosphate buffer of pH 6.9, 50 μl of amylase and analyte at different concentrations as 100, 250 and 500 μg were incubated at 37 0 C for 10 min. After pre-incubation, 500 μl of 1% (w/v) starch solution in the above buffer was added to each tube and incubated at 37 0 C for 15 min.…”

The role of phytochemicals in modulating intrinsic human cellular defence processes

“…One study claimed to be using a broccoli sprout BSE but the Supplementary Materials describing the material showed that it was, in fact a dried whole broccoli sprout powder. 198 Daily doses of SFN in these studies ranged from (Table 7.1).…”

“…198 Chapter 7 described the process for determination of dosage in the EASYGENEX Study. In summary, histone deacetylation (HDAC) is known to be inhibited by an Nrf2-unrelated mechanism and typically responds to higher doses than for Nrf2…”