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HM-Chromanone, a Major Homoisoflavonoid in Portulaca oleracea L., Improves Palmitate-Induced Insulin Resistance by Regulating Phosphorylation of IRS-1 Residues in L6 Skeletal Muscle Cells
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HM-Chromanone, a Major Homoisoflavonoid in Portulaca oleracea L., Improves Palmitate-Induced Insulin Resistance by Regulating Phosphorylation of IRS-1 Residues in L6 Skeletal Muscle Cells
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HM-Chromanone, a Major Homoisoflavonoid in Portulaca oleracea L., Improves Palmitate-Induced Insulin Resistance by Regulating Phosphorylation of IRS-1 Residues in L6 Skeletal Muscle Cells
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Journal Article
HM-Chromanone, a Major Homoisoflavonoid in Portulaca oleracea L., Improves Palmitate-Induced Insulin Resistance by Regulating Phosphorylation of IRS-1 Residues in L6 Skeletal Muscle Cells
2022
Overview
This study investigated the effect of (E)-5-hydroxy-7-methoxy-3-(2-hydroxybenzyl)-4-chromanone (HM-chromanone) on palmitate-induced insulin resistance and elucidated the underlying mechanism in L6 skeletal muscle cells. Glucose uptake was markedly decreased due to palmitate-induced insulin resistance in these cells; however, 10, 25, and 50 µM HM-chromanone remarkably improved glucose uptake in a concentration-dependent manner. HM-chromanone treatment downregulated protein tyrosine phosphatase 1B (PTP1B) and phosphorylation of c-Jun N-terminal kinase (JNK) and inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), which increased because of palmitate mediating the insulin-resistance status in cells. HM-chromanone promoted insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and suppressed palmitate-induced phosphorylation of IRS-1 serine. This activated phosphoinositide 3-kinase (PI3K) and stimulated protein kinase B (AKT) phosphorylation. Phosphorylated AKT promoted the translocation of Glucose transporter type 4 to the plasma membrane and significantly enhanced glucose uptake into muscle cells. Additionally, HM-chromanone increased glycogen synthesis through phosphorylating glycogen synthase kinase 3 alpha/beta (GSK3 α/β) via AKT. Consequently, HM-chromanone may improve insulin resistance by downregulating the phosphorylation of IRS-1 serine through inhibition of negative regulators of insulin signaling and inflammation-activated protein kinases in L6 skeletal muscle cells.
Publisher
MDPI AG,MDPI
Subject
/ Diabetes
/ Glucose
/ Glucose Transporter Type 4 - metabolism
/ glycogen
/ Glycogen Synthase Kinase 3 - metabolism
/ Humans
/ I-kappa B Kinase - metabolism
/ insulin
/ insulin receptor substrate proteins
/ Insulin Receptor Substrate Proteins - metabolism
/ Insulin Resistance - physiology
/ JNK Mitogen-Activated Protein Kinases - metabolism
/ Kinases
/ mitogen-activated protein kinase
/ Muscle, Skeletal - metabolism
/ muscles
/ NMR
/ non-specific serine/threonine protein kinase
/ phosphatidylinositol 3-kinase
/ Phosphatidylinositol 3-Kinase - metabolism
/ Phosphatidylinositol 3-Kinases - metabolism
/ Plasma
/ Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism
/ protein-tyrosine-phosphatase
/ Proteins
/ Proto-Oncogene Proteins c-akt - metabolism
/ serine
/ tyrosine
