HM-chromanone, a component of Portulaca oleracea L., stimulates glucose uptake and glycogen synthesis in skeletal muscle cell

Abstract

BackgroundDiabetes mellitus is a chronic metabolic disease characterized by increased blood glucose levels. In order to lower blood glucose, it is important to stimulate glucose uptake and glycogen synthesis in the muscle. (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone (HM-chromanone), a constituent isolated from Portulaca oleracea L., exhibits anti-diabetic effects; however, its mechanisms are not yet clearly understood on glucose uptake and glycogen synthesis in muscle cells. PurposeIn the present study, we examined the effects of HM-chromanone on glucose uptake into L6 skeletal muscle cells and elucidated the underlying mechanisms. MethodsThe effects of HM-chromanone on glucose uptake into L6 skeletal muscle cells were assessed by 2-Deoxyglucose uptake assay. Western blot analysis was carried out to elucidate the underlying molecular mechanisms. ResultsWe found that HM-chromanone promoted glucose uptake into L6 skeletal muscle cells in a dose-dependent manner. Moreover, HM-chromanone induced the phosphorylation of IRS-1Tyr612 and AKTSer473, and the activation of PI3K. HM-chromanone also stimulated the phosphorylation of AMPKThr172, AS160Thr642, TBC1D1Ser237, and ACC via the CaMKKβ pathway. Furthermore, HM-chromanone increased glycogen synthesis through the inactivation of glycogen synthase kinase 3 α/β. ConclusionThe results of this study indicate that HM-chromanone stimulates glucose uptake through the activation of the PI3K/AKT and CaMKKβ-AMPK pathways and glycogen synthesis via the GSK3 α/β pathway in L6 skeletal muscle cells.