Ethnopharmacological relevance:The radix ofAcorus calamusL. (AC) is widely used in diabetes therapies in
traditional folk medicine from America and Indonesia, and we have previously reported that the ethyl acetate
fraction of AC (ACE) acts as an antidiabetic through insulin sensitizing, insulin releasing and alpha-glucosidase
inhibitory activities. The present study is designed to investigate the effects and molecular mechanisms of ACE
on glucagon-like peptide-1 (GLP-1) expression and secretion related to its hypoglycemic effects.
Materials and methods:The hypoglycemic effect of ACE (100 mg/kg, i.g.) was confirmed by testing blood
glucose levels orviaoral glucose tolerance test (OGTT) in streptozotocin (STZ) induced hyperglycemic mice,
db/dbdiabetic mice and diet-induced obese (DIO) mice. Plasma insulin, GLP-1 levels and intestinal GLP-1
related gene expression were determined in STZ-induced anddb/dbdiabetic mice. Thein vitro effects of
ACE (12.5μg/ml) on the expression and secretion of GLP-1 were detected in NCI-H716 intestinal L-cells,
and the correlation between ACE and molecules in the Wnt signaling pathway was further explored.
Results:ACE (100 mg/kg) significantly lowered fasting blood glucose in STZ-induced anddb/dbdiabetic mice
and improved the OGTT in DIO mice. Insulin releasing and islet protective effects, along with the increased
secretion of GLP-1, were observed. The expression of proglucagon gene (gcg) and post-translational
processing gene prohormone convertase 3 (pc3) and the GLP-1 content in the culture medium of L-cells
notably increased after the ACE treatment (12.5μg/ml). At the same time,β-catenin nuclear translocation
occurred, and its downstream protein cyclin D1 was activated, showing the involvement of Wnt signaling.
Conclusions:ACE might activate Wnt signaling to increase the gene expression ofgcgandpc3and exert
incretin effects, including insulinotropic and islet protection, to lower blood glucose levelsviaelevated GLP-1
secretion either directly or indirectly