Modified Si-Miao-San ameliorates pancreatic B cell dysfunction by inhibition of reactive oxygen species-associated inflammation through AMP-kinase activation

AIM： To observe the effect of modified Si-Miao-San （mSMS） on advanced glycation end products （AGEs）-induced pancreatic B cell dysfunction, as well as examining the underlying mechanisms.METHOD： Pancreatic B cells （INS-l） were stimulated with advanced glycation end products （AGEs, 200 μg.mL^-1） for 24 h to produce dysfunction in pancreatic B cells and the effects of mSMS observed on insulin secretion, NF-κB （p65） phosphorylation, reactive oxygen species （ROS） production, mitochondria membrane potential （△ψm）, cell apoptosis, phosphorylation of AMP-kinase （AMPK）, and caspase 3 activity. RESULTS： The AGEs challenge resulted in increased basal insulin secretion, but decreased insulin secretion in response to high glucose, whereas this situation was reversed by mSMS treatment. AGEs stimulation induced NF-κB （p65） phosphorylation and reactive oxygen species （ROS） production, as well as Agtm collapse and cell apoptosis, mSMS inhibited ROS production and inhibited NF-κB activation by attenuating p65 phosphorylation. Meanwhile, AGEs-induced A^m collapse and cell apoptosis were also reversed by mSMS treatment. Compound C, an inhibitor of AMP-Kinase （AMPK）, abolished the beneficial effects of mSMS on the regulation of B cell fimction, indicatin~ the involvement of AMPK. cONCLUSION： mSMS ameliorated AGEs-induced B cell dysfimction by suppressing ROS-associated inflammation, and this action was related to its beneficial regulation of AMPK activity.

AIM: To observe the effect of modified Si-Miao-San(mSMS) on advanced glycation end products(AGEs)-induced pancreatic B cell dysfunction, as well as examining the underlying mechanisms. METHOD: Pancreatic B cells(INS-1) were stimulated with advanced glycation end products(AGEs, 200 μg·mL-1) for 24 h to produce dysfunction in pancreatic B cells and the effects of mSMS observed on insulin secretion, NF-κB(p65) phosphorylation, reactive oxygen species(ROS) production, mitochondria membrane potential(Δψm), cell apoptosis, phosphorylation of AMP-kinase(AMPK), and caspase 3 activity. RESULTS: The AGEs challenge resulted in increased basal insulin secretion, but decreased insulin secretion in response to high glucose, whereas this situation was reversed by mSMS treatment. AGEs stimulation induced NF-κB(p65) phosphorylation and reactive oxygen species(ROS) production, as well as Δψm collapse and cell apoptosis. mSMS inhibited ROS production and inhibited NF-κB activation by attenuating p65 phosphorylation. Meanwhile, AGEs-induced Δψm collapse and cell apoptosis were also reversed by mSMS treatment. Compound C, an inhibitor of AMP-Kinase(AMPK), abolished the beneficial effects of mSMS on the regulation of B cell function, indicating the involvement of AMPK. CONCLUSION: mSMS ameliorated AGEs-induced B cell dysfunction by suppressing ROS-associated inflammation, and this action was related to its beneficial regulation of AMPK activity.