Effects And Mechanism Of Water Extract Of Malus Toringoides(Rehd.)hughes.on Glucose Metabolism In Streptozotozin-induced Diabetic Mice

Objective:The hypoglycemic effect and possible mechanism of water extract from Malus toringoides(Rehd.)Hughes were investigated from the aspects of blood glucose,blood lipid and pancreatic islet function by intraperitoneal injection of STZinduced diabetic mice.Methods:Buy healthy kunming(KM)mice to 150,18-20 g weight,male and female half,adaptability to feed a week later,the reserved 12 as normal control group,the rest of the mice by 50 mg/kg for 10 days to the intraperitoneal injection of STZ,after intraperitoneal injection of the last to fast but drink after 16 hours cut tail blood test mice fasting blood glucose(FBG),when the FBG acuity 11.1 tendency/L think building success.The model mice were randomly divided into 6 groups according to their blood glucose values,namely: model control group,rosiglitazone group,BYHT0.75 g/kg group,BYHT1.50 g/kg group,BYHT3.00 g/kg group,and BYHT6.00 g/kg group.All mice were given 10 ml/kg orally,the normal control group and the model control group were given distilled water orally,the rosiglitazone group was given rosiglitazone(2.67mg/kg/d)solution orally,and the BYHT four groups were given different doses of BYHT water extract extract solution(0.75,1.50,3.00,6.00g/kg/d)from low to high.The drug was administered continuously for 38 days.During the experiment,the weight and FBG of the mice were measured at a fixed time every week.ITT was measured on day 32 and OGTT was measured on day 35.At the end of the experiment,the eyeball was removed and the fasting blood was taken,the serum was separated,and TG,TC,HDL-C,LDL-C,GSP,FINS,glucagon and GLP-1 were detected.The pancreatic tissue was isolated and fixed with 4% paraformaldehyde solution.The histopathological changes of the pancreas were observed by HE staining,and the apoptosis of islet cells was observed by TUNEL staining.Results:Compared with the normal control group,the weight of the model control group was significantly reduced and the fasting blood glucose level was significantly increased(P<0.01).ITT and OGTT increased blood glucose at each time point(P<0.01 or P<0.05).The contents of TG,TC,LDL-C and GSP in serum were significantly increased(P<0.01).The content of serum FINS and GLP-1 decreased significantly(P < 0.01),and the content of glucagon increased slightly,but the difference was not significant(P > 0.05).HOMA-IR significantly increased and HOMA-β significantly decreased(P<0.01).The pancreatic tissue of model control group showed obvious cell degeneration,vacuole and necrosis,and the apoptosis rate of islet cells increased(P<0.01).Compared with the model control group,the body weight of the mice in each dose group of BYHT increased slightly,but there was no statistical difference(P>0.05).Compared with the model control group,the fasting blood glucose of the mice in each dose group of BYHT at the 2nd,3rd,4th and 5th week of administration was significantly reduced(P<0.01 or P<0.05).Compared with the model control group,the blood glucose values of the mice in each dose group of BYHT at ITT and OGTT all decreased to different degrees(P<0.01 or P<0.05).Compared with model control group,TG,TC,GSP serum of BYHT each dose group mice content is slightly lower,but no significant statistical difference(P>0.05),LDLC of BYHT each dose group mice serum content is lower,at 1.50,3.00g/kg dose group of LDL-C serum values were decreased significantly(P<0.05 or P<0.01),the water extract of BYHT dose group mice serum content of HDL-C slightly raised,but no significant statistical difference(P>0.05);Compared with the model control group,serum GLP-1 was slightly increased in each water extract group,while serum Glucagon content was slightly decreased in the dose groups of 3.00 and 6.00 g/kg,but the statistical difference was not significant(P>0.05).The serum FINS of the mice in each water extract group of BYHT were increased,and the dose of BYHT at 6.00g/kg was significant in the group(P<0.05).The levels of HOMA-β in each water extract group were increased,and the dose groups of 3.00 and 6.00g/kg were significantly higher(P<0.05).The reduction of HOMA-IR in each water extract group was more significant in the 1.50g/kg dose group(P<0.05).Compared with the model control group,the degree of degeneration and necrosis of pancreatic cells and/or islet cells was improved and the apoptosis rate of pancreatic cells was reduced in the dose groups of BYHT.The apoptosis rates of the dose groups of malus variegatus 1.50 and 6.00g/kg were significantly reduced,and the statistical differences were significant(P<0.01 or P<0.05).Conclusion:BYHT can significantly improve glucose and lipid metabolism in STZ-induced diabetic model mice,and its mechanism may be related to the protection and/or repair of islet tissue function,inhibition of islet cell apoptosis,promotion of insulin secretion and improvement of insulin resistance.