Anti-diabetic Effect And Mechanism Of Geniposide

Objective:1.To study the effect of geniposide on insulin secretion in INS-1 cells and rat pancreatic islets treated with high glucose and palmitate.2.To investigate the action of geniposide on the proliferation and apoptosis treated with high glucose and palmitate in INS-1 cells.3.To study the anti-diabetic effect of geniposide in db/db mice.Methods:1.Using enzyme-linked immunosorbent assay(ELISA)method to detect insulin levels under different conditions.2.Using molecular docking method to detect the binding ability of geniposide and GLP-1 receptor.3.The cell proliferation/ toxicity detection method(CCK-8)and flow cytometry were respectively used to detect the viability and apoptosis rate in INS-1 cells.4.Eight-week old db/ db mice with a C57BL/ 6N background were divided into 2groups(n = 10 in each group): model group and experimental group.C57BL/ 6N mice were set up as control group.The experimental group was intraperitoneally injected with geniposide 200 mg/kg/d.The control group and model group were intraperitoneally injected with equal volume of normal saline for 11 weeks.The fasting blood glucose was measured using a glucometer every week.Body weight was measured every week.At the end of the intervention in week 11,the intraperitoneal glucose tolerance test(IPGTT)and the intraperitoneal insulin tolerance test(IPITT)were performed and PET-CT was used to detect the body fat of the mice.The pancreases of mice were isolated and stained with hematoxylin-eosin(HE).The liver and kidney were removed and weighed.Blood was collected for determination of superoxide dismutase(SOD),glutathione(GSH),alanine aminotransferase(ALT),aspartate aminotransferase(AST),total protein(TP),albumin(ALB),globulin(GLB),total bilirubin(TBIL),urea nitrogen(Urea),creatinine(CRE),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDLC)and high-density lipoprotein cholesterol(HDLC).Results:1.Geniposide promoted insulin secretion in INS-1 cells(P<0.01).Geniposide promote insulin secretion in C57BL/6N mice and lower blood sugar(P<0.05).Geniposide improved insulin secretion in INS-1 cells and rat islets treated with high glucose and palmitate through GLP-1 receptors(P<0.001 and P<0.01).Geniposide had a strong binding effect with GLP-1 receptor.2.Geniposide promoted the proliferation in INS-1 cells(P<0.05),inhibited high glucose and palmitate or Thapsigargin-induced apoptosis in INS-1 cells acting through the GLP-1 receptor(P<0.05 and P<0.01).3.Geniposide had anti-diabetic effect on db/db mice.Geniposide reduced fasting blood glucose(P<0.05),glycated hemoglobin(P<0.05),increased insulin sensitivity(P<0.05),improved glucose tolerance(P<0.01,P<0.05 and P<0.05 at 0,5 and 15min),reduced insulin resistance(P<0.05),protected islets morphology and reduced body weight(P<0.05)and body fat(P<0.01)in db/db mice.Geniposide improved the oxidative stress state(P<0.05)and had no effect on blood lipids,liver function and kidney function in db/db mice.Geniposide promoted intestinal peristalsis in C57BL/6N mice(P<0.01).Conclusion:Geniposide improved insulin secretion in INS-1 cells and C57BL/6N mice and rat pancreatic islets treated with high glucose and palmitate and promoted proliferation and inhibited apoptosis in INS-1 cells.Geniposide had antidiabetic effects on db/db mice.Geniposide was safe for mice with long-term application.In the study,the effects of geniposide on β-cells function and morphology under physiological and pathological conditions were investigated at three levels: cells,islets,and diabetic mice.Geniposide had the typical biological characteristics of GLP-1 receptor agonists.Our study provided the theoretical basis for the development and application of geniposide.