Impact of oridonin on insulin resistance in rats with impaired glucose tolerance by regulating the JAK2/STAT3/SOCS-1 signaling pathway
Objective To investigate the impact of oridonin(Ori)on insulin resistance(IR)in rats with impaired glucose tolerance(IGT)and the underlying mechanism.Methods A high-fat diet combined with streptozotocin injection was used to construct an IR model of IGT rats.The rats were grouped into normal group(CT group),IGT model group(IGT group),Ori group(10mg·kg-1·d-1),and Ori+Colivelin(COL)group(10mg·kg-1·d-1 Ori+2mg/kg COL),with 6 rats per group.The fasting blood glucose(FPG)was measured using a glucose meter.The oral glucose tolerance test(OGTT)was performed to test the 2-hour plasma glucose(2hPG).Relative levels of fasting insulin(FINS),monocyte chemotactic protein-1(MCP-1),and tumor necrosis factor-α(TNF-α)were measured by enzyme-linked immunosorbent assay(ELISA).The homeostatic model assessment for insulin resistance(HOMA-IR)was calculated.Serum cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected using an automatic analyzer.The hematoxylin and eosin(H&E)staining was applied to observe the pathological morphology of the liver.Western blot was applied to detect the protein expressions of phosphorylated Janus kinase 2(p-JAK2),JAK2,phosphorylated signal transducer and activator of transcription 3(p-STAT3),STAT3,phosphorylated suppressor of cytokine signaling 1(p-SOCS-1),and SOCS-1.Results Compared with those of the CT group,rats in IGT group presented swollen liver cells,abundant fat vacuoles of varying sizes in the cytoplasm,squeezing and displacement of nucleus by fat vacuoles,infiltration of inflammatory cells,significantly higher levels of FPG,2hPG,FINS,HOMA-IR,TC,TG,LDL-C,MCP-1,TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 and p-SOCS-1/SOCS-1,and lower serum HDL-C(P<0.05).Compared with those of the IGT group,rats in the Ori group presented significantly fewer fat droplets and vacuoles,alleviated cell swollen,absence of inflammatory cells,significantly lower levels of FPG,2hPG,FINS,HOMA-IR,TC,TG,LDL-C,MCP-1,TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 and p-SOCS-1/SOCS-1,and higher serum HDL-C(P<0.05).Compared with those of Ori group,rats in Ori+COL group presented aggravated liver steatosis,cell swollen,significantly higher levels of FPG,2hPG,FINS,HOMA-IR,TC,TG,LDL-C,MCP-1,TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 and p-SOCS-1/SOCS-1,and lower serum HDL-C(P<0.05).Conclusion Ori alleviates IR in IGT rats by inhibiting the JAK2/STAT3/SOCS-1 signaling pathway.
impaired glucose toleranceinsulin resistanceoridoninJanus activated kinase 2/signal transducer and activator of transcription 3suppressor of cytokine signaling 1
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