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.
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