Flavone Hispidulin Stimulates Glucagon-Like Peptide-1 Secretion and Ameliorates Hyperglycemia in Streptozotocin-Induced Diabetic Mice

Mol Nutr Food Res. 2020 Mar;64(6):e1900978. doi: 10.1002/mnfr.201900978. Epub 2020 Feb 3.


Scope: Loss of functional β-cell mass is central for the deterioration of glycemic control in diabetes. The incretin hormone glucagon-like peptide-1 (GLP-1) plays a critical role in maintaining glycemic homeostasis via potentiating glucose-stimulated insulin secretion and promoting β-cell mass. Agents that can directly promote GLP-1 secretion, thereby increasing insulin secretion and preserving β-cell mass, hold great potential for the treatment of T2D.

Methods and results: GluTag L-cells, INS832/13 cells, and mouse ileum crypts and islets are cultured for examining the effects of flavone hispidulin on GLP-1 and insulin secretion. Mouse livers and isolated hepatocytes are used for gluconeogenesis. Streptozotocin-induced diabetic mice are treated with hispidulin (20 mg kg-1 day-1 , oral gavage) for 6 weeks to evaluate its anti-diabetic potential. Hispidulin stimulates GLP-1 secretion from the L-cell line, ileum crypts, and in vivo. This hispidulin action is mediated via activation of cyclic adenosine monophosphate/protein kinase A signaling. Hispidulin significantly improves glycemic control in diabetic mice, concomitant with improved insulin release, and β-cell survival. Additionally, hispidulin decreases hepatic pyruvate carboxylase expression in diabetic mice and suppresses gluconeogenesis in hepatocytes. Furthermore, hispidulin stimulates insulin secretion from β-cells.

Conclusion: These findings suggest that Hispidulin may be a novel dual-action anti-diabetic compound via stimulating GLP-1 secretion and suppressing hepatic glucose production.

Keywords: diabetes; glucagon-like peptide-1; hispidulin; insulin; mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Eating / drug effects
  • Flavones / pharmacology*
  • Glucagon-Like Peptide 1 / metabolism*
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / metabolism
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Male
  • Mice, Inbred C57BL


  • Flavones
  • Hypoglycemic Agents
  • Insulin
  • Glucagon-Like Peptide 1
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • hispidulin