Overexpression Of Parathyroid Hormone-related Protein Ameliorate High-fat Diet Induced Mouse Islets Apoptosis

Background and Purpose:Due to the changes in the diet and lack of exercise,the incidence of obesity and type 2 diabetes is increasing among all the population,and there is an urgent need for better treatments and cures for obesity and type 2 diabetes.It is estimated that there were 366 million adults aged 20-79 worldwide in 2011,coverd 8.3%of all the populations,and this number is expected to rise to 552 million(9.9%)by 2030..Although the current researches have a certain understanding of the pathogenesis of type 2 diabetes,It is still far for us to find the cure for type 2 diabetes,millions of people are still suffer from diabetes and its complications.The domestic and international fundings for obesity,metabolic syndrome and diabetes are increasing year by year makes more and more scholars participate in the related researches.In addition to genetic factors,the relationship between metabolism and reproduction,intestinal flora,and tumor immunity has been revealed.Since the islets can secretion the only down regulation hormone-insulin,more and more studies are focusing on the islets.Parathyroid Hormone-related Protein(PTHrP)is a member of the parathyroid hormone family,it plays an important role in maintaining many physiological functions in the body.In our previous studies,we found that Parathyroid Hormone-related Protein(PTHrP)promotes the progression of liver injury,and the formation of liver fibrosis,.In the mice model we injection AAV-PTHrP though the tail vein,we found that there are significant weight loss in the PTHrP mice.In order to explore the causes and the possible role of PTHrP in obesity and metabolic syndrome,we investigated the effect of PTHrP on apoptosis of islet cells in mice fed with high-fat diet.Methods:1.6-8 weeks old C57BL/6 mice was injected with AAV-PTHrP and fed with high-fat diet for 8 weeks.Body weight was measured;2.The insulin level among with fed and fasting blood glocuse level was measured from the tail vein and GTT(2g/kg)was also performed;3.After 10 weeks of high-fat diet,the mice were starved for 6 hours,then the mice were sacrificed and the pancreatic tissues were collected as soon as possible.The changes of apoptosis-related genes Bcl2 and Bax were detected by WB,QPCR and immunohistochemistry;4.Pancreatic tissues were tested for TUNEl staining.Results and Concluions:1.After 8 weeks high-fat diet,mouse islets showed a obvious apoptotic response,the proportion of apoptotic cells increased,while the apoptosis of mouse islet was significantly reduced.Moreover,WB,QPCR and immunohistochemistry share the same trend;2.PTHrP mice showed lower body weight,better glucose tolerance,and lower random and fasting blood glucose levels,means that PTHrP can help prevent MS caused by high-fat diet.