Effects Of Ursodeoxycholic Acid On Blood Glucose、Islet Function And Liver Lipid Deposition In Rats With Type 2 Diabetes

Objective:To investigate the effects of ursodeoxycholic acid on blood glucose,islet function and liver lipid deposition in rats with type 2 diabetes.Methods:Eighteen male SD rats were randomly divided into three groups: group A(normal group,n=6),group B(type 2 diabetes model group,n=6),group C(intervention group,n=6)on the basis of group B,and ursodeoxycholic acid intervention.In this experiment,it is proposed to use streptozotocin combined with high-fat feed to create a rat model of type 2 diabetes.For 1～4weeks of experiment,group A was fed conventional ordinary feed,and groups B and C were fed60% fat energy high-fat feed to induce insulin resistance.After 4 weeks,group A was intraperitoneally injected with sterile citrate buffer(p H 4.4),and group B and C were intraperitoneally injected with streptozotocin(STZ,formulated with sterile citrate buffer(p H 4.4)and ready to use)at a dose of 30 mg/kg,injected once.In the fifth week of the experiment,group C was given ursodeoxycholic acid by transesophageal gavage at an intervention dose of 0.25%of the food intake once a day for 8 weeks.The changes of general condition,body weight and blood glucose of each group were observed weekly,and glucose tolerance test(OGTT)was performed after 12 weeks,and insulin and C-peptide release tests were measured at 0h,1h,and2 h,respectively.At the end of 12 months,rats were processed and collected,serum ALT,AST,LDL,GGT,ALP,triglycerides and total cholesterol concentrations were measured,and pancreas and liver tissues were retained,and Hematoxylin-eosin(HE)staining was performed to observe the morphological changes of pancreas,and triglycerides and cholesterol concentrations in the liver were determined;Results:1.General situation: In the 8th week of intraperitoneal injection of streptozotocin combined with high-fat diet,compared with group A,rats in group B had increased food intake and water intake,increased urine output,decreased activity.The rats in group C started to intervene from the5 th week.Compared with group B,the amount of food and water consumed in group C was less than that of group B,the urine output decreased,and the activity gradually increased.Glucose metabolism indicators: group A’s fasting blood sugar fluctuated at 4.6 to 5.8mmol/L,1h blood sugar fluctuated at 5.5 to 7mmol/L,and 2h blood sugar fluctuated at 6.6 to 7.8mmol/L;fasting insulin fluctuated at 13.82 to 15.94 m IU/L,1h Insulin fluctuated at 28.69 to 40.98 m IU/L,2h insulin fluctuated at 15.76 to 24.17 m IU/L;fasting C-peptide fluctuated at 124.30 to134.91pmol/L,1h C-peptide fluctuated at 168.61 to 188.15pmol/L,2h C-peptide fluctuated at118.70 to 128.72pmol/L.Compared with group A,the fasting blood glucose in group B fluctuated from 9.3 to 10.7mmol/L,the 1h blood glucose fluctuated from 10.1 to 12.6mmol/L,the 2h blood glucose fluctuated from 11.2 to 13.0mmol/L,and the OGTT increased significantly at each time point(P <0.05);the fasting insulin fluctuated from 12.43 to 14.91 m IU/L,the 1h insulin fluctuated from 28.58 to 35.96 m IU/L,and the 2h insulin fluctuated from 15.48 to22.09 m IU/L.Compared with group A,the fasting and 1h insulin concentrations of group B significantly decreased(P<0.05);the fasting C-peptide fluctuated in 119.69 to 125.19pmol/L in group B,the 1h C-peptide fluctuated in 167.33 to 176.56pmol/L,and the 2h C-peptide fluctuated in 115.36 to 120.67pmol/L.Compared with group A,the C-peptide concentrations of group B at each time point decreased significantly(P<0.05).Compared with group B,group C’s fasting blood glucose fluctuated in 7.9 to 9.2mmol/L,1h blood glucose fluctuated in 10.4 to 11.8mmol/L,2h blood glucose fluctuated in 9.7 to 11.1mmol/L,fasting and 2h blood glucose decreased significantly(P<0.05);the fasting insulin fluctuated from 13.97 to 16.16 m IU/L,the 1h insulin fluctuated from 31.44 to 37.60 m IU/L,and the 2h insulin fluctuated from 19.03 to 25.98 m IU/L.Compared with group B,the insulin concentration at each time point in group C increased significantly(P<0.05);C-peptide fluctuated from 125.09 to 131.96 pmol/L on an empty stomach in group C,165.95 to 173.61 pmol/L at 1h,and 110.16 to 119.0 pmol/L at 2h.Compared with group B,The concentration of C-peptide at each time point in group C was significantly increased(P<0.05).Biochemical indicators: Compared with group A,ALT,AST,LDL,GGT,ALP,triglyceride,and total cholesterol in group B were significantly increased(P<0.05);compared with group B,ALT,GGT,LDL,ALP,triglyceride,total cholesterol levels in group C were significantly reduced(P<0.05),AST levels did not change significantly(P>0.05).Compared with group A,triglyceride and total cholesterol in liver tissue of group B were significantly increased(P<0.05);compared with group B,triglyceride and total cholesterol in liver tissue of group C were significantly lower(P<0.05).2.Pathological results: pancreatic HE pathology: the exocrine part of the pancreas and islet cells of group A were arranged neatly,the structure was complete;Compared with group A,the islet cells in group B were arranged in disorder,the morphology was irregular,the number of islets and islet area was significantly reduced(P<0.05).Compared with group B,group C had irregular islet morphology,increased the number of islets and islet area(P<0.05).Conclusion:Inflammatory reactions can occur in pancreatic tissue in rats with type 2 diabetes,liver lipid deposition and insulin resistance,which increases blood sugar.Ursodeoxycholic acid intervention can improve blood glucose and insulin resistance,reduce serum and liver triglyceride and total cholesterol levels,and improve hepatic fat deposits.