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

Annika S Axelsson1, Emily Tubbs1, Brig Mecham2

  • 1Department of Clinical Sciences, Lund University Diabetes Center, Malmö, SE-20502 Malmö, Sweden.

Science Translational Medicine
|June 16, 2017
PubMed

Insights

Sulforaphane, a compound found in broccoli sprouts, may reverse type 2 diabetes signatures. Clinical trials showed it reduced blood glucose and HbA1c in diabetic patients.

Area of Science:

  • Biochemistry
  • Genomics
  • Pharmacology

Background:

  • Connecting disease and drug gene expression profiles is a promising drug discovery strategy.
  • Type 2 diabetes signatures in liver tissue require identification for targeted therapeutic development.

Purpose of the Study:

  • To identify a disease signature for type 2 diabetes in liver tissue.
  • To screen drug signatures for compounds that can reverse the identified type 2 diabetes signature.
  • To evaluate the therapeutic potential of sulforaphane in preclinical models and human subjects.

Main Methods:

  • Analysis of coexpression networks and genetic data to establish a type 2 diabetes liver disease signature.
  • Interrogation of a 3800-drug signature library to identify potential therapeutic compounds.
  • In vitro studies on hepatic cells to elucidate sulforaphane's mechanism of action (NRF2 pathway).
  • In vivo studies in diabetic animal models to assess sulforaphane's efficacy in reversing disease signatures and improving glucose metabolism.
  • Clinical trial with obese patients with type 2 diabetes to evaluate sulforaphane's effect on fasting blood glucose and HbA1c.

Main Results:

  • A distinct disease signature for type 2 diabetes in liver tissue was identified.
  • Sulforaphane was identified as a compound capable of reversing the type 2 diabetes signature.
  • Sulforaphane suppressed hepatic glucose production via NRF2 nuclear translocation and reduced gluconeogenic enzyme expression.
  • Sulforaphane demonstrated efficacy comparable to metformin in diabetic animal models, improving glucose intolerance.
  • Oral administration of sulforaphane (broccoli sprout extract) significantly reduced fasting blood glucose and HbA1c in human patients.

Conclusions:

  • Sulforaphane effectively reverses type 2 diabetes signatures in liver tissue.
  • Sulforaphane exhibits therapeutic potential for type 2 diabetes, comparable to existing treatments.
  • Broccoli sprout extract containing sulforaphane represents a viable option for managing type 2 diabetes in obese patients.

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