Establishing Of The Old Fat Cynomolgus Monkey Diabetes Model

AIM:Diabetes Mellitus(DM)is an endocrine metabolism disease that is characterized by high incidence,difficult to cure,and multi-complication.Now,DM has become the third serious disease secondary to tumor and cardiovasvular disease which endanger human health seriously.But carrying on science research with patient directly is restricted to many factors,particularly the restriction of ethics.Hence it is necessary to establish the animal diabetes model for associated fundamental and application research.This study was done to eastablish cynomolgus's type 1 diabetes mellitus,the methods of establishing type 1 animal model of diabetes included operation,chemical injury,and virus infection,etc,the most commonly used was streptozotocin(STZ).Cynomolgus's type 1 diabetes mellitus having been established in China and other countrys didn't consider obesity,age and other diabetes's susceptible factors,in this study,the above factors were considered,meanwhile,diagnostic standard of cynomolgus monkey's DM was dicussed. The animal to establish type 1 animal model of diabetes included rats,mice and monkey. Rats,mice have low price,but they are different from human in hereditary characcterisic. Such as islet amyloid polypeptide(LAPP).LAPP as islet amyloid's endemic element was a kind of Polypeptide made of 37 Amino Acids,which was secreted by isletβ-cells.LAPP which only can be found in human,monkey,cat,raccoon has a close relation with DM.METHODSEight old fat cynomolgus monkeys(aged than 13 years old)were randomly assigned two groups(4 animal,model group,45mg/kg STZ and 4 animals in control group),the experimental animals were injected intravenously with 45mg/kg STZ after fasting for 16 hours(confecting 1%with 0.1mmol/l,pH4.2-4.5 citric acid solution before mainlining).The control monkeys were mainlined with the same dose of 0.1 retool/l,pH4.2-4.5 citric acid solution.For all monkeys,to test water intake,food intake,Spirit and urine everyday,to test body weight,blood glucose,urine glucose,triglyceride and cholesterol every week,to test C-peeptide and glutamic acid antibody and IV-GTT(Intravenous glucose tolerance test) twice,and to detect clinical index of diabetic monkeys and the development of diabetes mellitus.The pathological changes and histopathological observation of two animal's islet were made. RESULTThe model monkey's absorb,water intake and urination increased obviously and had statistial significance.Fasting blood glucose increased obviously,and urine sugar increase from Ommol/L to 2000mmol/L in the same time.Intravenous glucose tolerance test appeared abnormality in the fifth week.C-peptide(important index judging islet cells) decreased obviously,and glutamate decarboxylase antibody(which autoantibody I diabetic patients appear first.)changed from negative to masculine.Spirit,cholesterol total and triglyceride didn't show abnormal.The control group' s absorb,water intake and urination had no marked change or only change a little,and blood sugar,urine sugar,sugar tolerance were normal.CONCLUSIONThe study showed that cynomologus monkeys were resulted in IDDM disease animal model after STZ-inducing,Based on these findings,we propose that:(1)Fasting blood-glucose＞8.0mmol/L for at least in 3 weeks.Limosis means no eating in 8 hours.(2) In Intravenous glucose tolerance test,2h PG≥110.0mmol/L.If one of the above two items were found,the animal had suffered from Diabetes mellitus.If C-peptide decreased obviously,GAD--Ab changed from negative to masculine,the monkey had suffered from Type 1 Diabetes mellitus.