Impacts of geniposide on insulin resistance in pregnant diabetes rats by regulating HMGB1-RAGE signal pathway
Objective To investigate the impacts of geniposide on insulin resistance in pregnant diabetes rats by regulating high mobility group box 1-receptor for advanced glycation end products signaling pathway(HMGB1-RAGE signaling pathway).Methods Pregnant diabetes rats were grouped into control group,model group(GDM group),low dose of geniposide group(GP-L group,200 mg·kg1·d-1 GP),medium dose of geniposide group(GP-M group,400 mg·kg-1·d-1 GP),and high dose of geniposide group(GP-H group,500 mg·kg-1·d-1 GP),and HMGB1 inhibitor Glycyrrhizin group(Gly group).ELISA method was applied to detect the levels of IL-1β,IL-6,and TNF-α;kits were applied to measure the concentrations of fasting insulin(FINS),total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and serum GLUT4 and CTRP3 proteins;HE staining was applied to observe the histopathology changes of liver;PAS staining was applied to observe the expression of liver glycogen;Western blot was applied to determine the expression of HMGB1 and RAGE proteins.Results Compared with the Control group,the liver tissue structure in the GDM group was damaged,and fat deposition increased,the expression of liver glycogen(0.17±0.02)was obviously reduced(P＜0.05),the levels of IL-1β(35.34±3.52),IL-6(24.31±2.32),TNF-α(38.96±2.25),FBG(13.21±1.06),FINS(20.43±1.65),HOMA-IR(11.99±1.20),TC(3.11±0.56),TG(1.91±0.35),LDL-C(1.49±0.19),HMGB1(1.28± 0.13)和 RAGE(1.43±0.15),and the TG/HDL-C ratio(2.81±0.26)were obviously increased(P＜0.05),the levels of HDL-C(0.68±0.07),GLUT4(2.21±0.61)和 CTRP3(299.21±31.43)were obviously reduced(P＜0.05);compared with the GDM group,the liver tissue structure of the GP-L,GP-M,GP-H,and Gly groups was neat,with normal cell morphology and less fat deposition;the liver tissue was evenly stained and the expression of glycogen(0.31±0.04,0.44±0.03,0.56±0.05,0.59±0.07b)obviously increased(P＜0.05),and the drug treatment groups showed a dose-dependent increase(P＜0.05),the levels of IL-1 β(30.81±2.41,27.65±2.03,21.54±2.12,21.68±1.97),IL-6(21.05±1.28,17.35±1.04,12.37±1.16,12.69±1.05),TNF-α(32.17±2.03,29.18±1.74,22.69±1.41,23.17±1.12),FBG(11.86±1.19,9.38±1.06,7.07±1.14,6.96±1.08),FINS(17.06±1.37,14.60±1.16,11.03±1.25,11.76±1.11),HOMA-IR(8.99±1.22,6.07±0.91,3.47±0.43,3.64±0.14),TC(2.64±0.16,1.83±0.12,1.43±0.04,1.36±0.38),TG(1.67±0.21,1.41±0.19,1.17±0.23,1.20±0.11)和 LDL-C(1.36±0.16,1.17±0.13,0.96±0.06,0.87±0.04),HMGB1(0.94±0.10,0.54±0.05,0.35±0.07,0.30±0.2)和 RAGE(1.21±0.10,0.98±0.06,0.77±0.09,0.69±0.05),and the TG/HDL-C ratio(2.06±0.21,1.48±0.11,0.98±0.12,1.03±0.10)in the GP-L,GP-M,GP-H,and Gly groups were obviously reduced(P＜0.05),the levels of HDL-C(0.81±0.06,0.95±0.09,1.19±0.13,1.16±0.21),GLUT4(3.06±0.49,4.18±1.10,5.41±0.96,5.25±0.82),and CTRP3(362.43±30.27,427.25±45.41,481.16±44.23,473.53±41.38)were obviously increased,and the drug treatment groups showed a dose-dependent effect(P＜0.05).Conclusion Geniposide inhibits insulin resistance in pregnant diabetes rats by inhibiting HMGB1-RAGE signaling pathway.
GeniposideGestational diabetes mellitusHigh mobility group box 1-receptor for advanced glycation end productsInsulin resistance
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