Preliminary Study Of Rubus Polysaccharide Reducing Blood Glucose In Type 2 Diabetic Mice By Improving Pancreatic Mitochondrial Function

Objective To investigate the improvement effect of Rubus polysaccharide(RP)on pancreatic mitochondrial function of type 2 diabetes mellitus(T2DM)mice,and to provide new ideas and experimental basis for the development of mitochondria targeted T2 DM drugs.Methods1.Preparation of type 2 diabetes mice model70 C57BL/6J male mice were adaptively fed for 1 week,of which 10 mice were given normal diet as the normal control group(Control),and the remaining 60 mice were given high-fat diet as the model group(Model).After 4 weeks of high-fat diet feeding,mice in the Model group were injected intraperitoneally with streptozotocin(STZ)to induce the T2 DM mouse model.One week after the STZ model was established,the changes of general state(mental state,coat color and autonomous activity),body weight,drinking water and food intake of the mice were observed.The fasting blood glucose(FBG)and the homeostasis model assessment-insulin resistance(HOMA-IR)of the mice were detected.The mouse serum FBG≥7.8 mmol/L can be considered as successful preparation of the type 2 diabetes mouse model.2.Research on the hypoglycemic effect of RP50 mice were randomly selected from 52 mice with successful modeling and divided into 5 groups: Model group,low-dose group of RP(RPL),medium-dose group of RP(RPM),high-dose group of RP(RPH)and metformin group(Met).Each dose group of RP was gavaged with different concentrations of RP solution,the Met group was intragastrically administered equal volume of metformin solution,and the Control group and Model group were intragastrically administered equal volume of normal saline,once a day for 10 weeks.During the experiment,the general state of the mice was observed daily,the body weight and FBG of the mice were monitored weekly,and the mice were subjected to an oral glucose tolerance test(OGTT)every 4week.After the experiment,mouse plasma samples and fresh pancreatic tissue were collected to calculate the pancreatic index.The levels of fasting insulin(FINS),C-peptide and glucagon(GC)in serum were detected.3.Research on the hypoglycemic mechanism of RPADP/O,respiratory control rate(RCR),mitochondrial membrane potential(MMP),basal respiratory oxygen consumption,maximal respiratory oxygen consumption and reactive oxygen species(ROS)generation rate in pancreatic mitochondria of mice in various groups were assessed by O2 K cellular energy metabolism analysis system(O2K).The activities of catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and the content of malondialdehyde(MDA)in the pancreas of mice in various group were detected by biochemical kits.Histopathological changes of mouse pancreas were observed by H&E staining.Results RP significantly improved the general state of T2 DM mice(better mental state,glossy coat color,and enhanced autonomic activity);decreased water intake,food intake,FBG,and area under the curve(AUC)of OGTT;increased FINS level and decreased HOMA-IR;increased C-peptide level and pancreatic index,decreased GC level.RP significantly increased ADP/O,RCR,MMP,basal respiratory oxygen consumption and maximal respiratory oxygen consumption;increased CAT,SOD and GSH-Px activities,decreased ROS generation rate and MDA content;increased the number and area of pancreatic islets and reduced inflammatory cell infiltration.Conclusion RP can significantly reduce blood glucose and regulate glucose metabolism in T2 DM mice.Its mechanism may be to improve pancreatic mitochondrial function,reduce pancreatic oxidative stress injury and improve islet cell function,so as to promote insulin secretion.