Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR b...Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR by reducing inflammation.Here,we report that isobavachromene(IB),a flavonoid derived from Psoralea corylifolia Linn.,ameliorates IR in 3T3-L1 adipocytes by inhibiting the mitogen-activated protein kinase(MAPK)and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.We first found that IB could promote glucose uptake in 3T3-L1 adipocytes by activating the phosphoinositide 3-kinase(PI-3K)/protein kinase B(Akt)signaling pathway and was more effective than the positive control sodium orthovanadate at concentrations ranging from 25 to 100μmol/L.Additionally,IB inhibited RAW264.7 macrophage infiltration into 3T3-L1 adipocytes and suppressed the secretion of inflammatory factors from RAW264.7 macrophages,as well as the phosphorylation levels of key proteins(NF-κB p65,extracellular-signal-regulated kinase 1/2(ERK1/2),Jun N-terminal kinase(JNK),and mitogen-activated protein kinase 38(p38))in the NF-κB and MAPK signaling pathways.In summary,IB improves glucose uptake in IR adipocytes,activates the PI-3K/Akt signaling pathway,inhibits the JNK and NF-κB inflammatory signaling pathways,and reduces adipocyte inflammation,thereby improving of IR in 3T3-L1 adipocytes.展开更多
基金supported by National Key R&D Program of China(2022YFF1100300)the Central Guidance on Local Science and Technology Development Found of Shenzhen,China(2021Szvup030).
文摘Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR by reducing inflammation.Here,we report that isobavachromene(IB),a flavonoid derived from Psoralea corylifolia Linn.,ameliorates IR in 3T3-L1 adipocytes by inhibiting the mitogen-activated protein kinase(MAPK)and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.We first found that IB could promote glucose uptake in 3T3-L1 adipocytes by activating the phosphoinositide 3-kinase(PI-3K)/protein kinase B(Akt)signaling pathway and was more effective than the positive control sodium orthovanadate at concentrations ranging from 25 to 100μmol/L.Additionally,IB inhibited RAW264.7 macrophage infiltration into 3T3-L1 adipocytes and suppressed the secretion of inflammatory factors from RAW264.7 macrophages,as well as the phosphorylation levels of key proteins(NF-κB p65,extracellular-signal-regulated kinase 1/2(ERK1/2),Jun N-terminal kinase(JNK),and mitogen-activated protein kinase 38(p38))in the NF-κB and MAPK signaling pathways.In summary,IB improves glucose uptake in IR adipocytes,activates the PI-3K/Akt signaling pathway,inhibits the JNK and NF-κB inflammatory signaling pathways,and reduces adipocyte inflammation,thereby improving of IR in 3T3-L1 adipocytes.