The Influence Of The Mammalian Target Of Rapamycin Pathway Changes On Islet β Cell Number In The Rats Under Chronic Intermittent Hypoxia

Objective: To investigate the influence of the changes the mammalian target of rapamycin(m TOR) pathway on islet β cell number in the rats under chronic intermittent hypoxia(CIH).Methods: Eighteen adult male Sprague-Dawley(SD) rats were randomly and meanly divided into 3 groups, including the normoxic group(group A), the CIH group(group B) and the CIH + rapamycin group(group C). The group A was fed at atmospheric pressure and air environment cabins. The group B and C were fed in the cabins with low oxygen conditions(60s/air, 60s/N2, filling alternately, guarantee the oxygen concentration in cabins fluctuating between 5% and 21%). The group C received intraperitoneal injection of rapamycin which was dissolved in the DMSO in 0.2 mg/kg/day. The group A and B received the mixure of DMSO and PBS with the same volume as group C. The intermittent hypoxia time each day was from 8:30 to 16:30. After 5 weeks, immunofluorescent staining was performed to detect the expression of m TOR/ p-S6/ e IF4 E. Insulin positive area and β cell number per islet were measured by the Image-Pro Plus software. Besides, we detected the serum insulin level by ELISA. We tested the normality and the homogeneity of variance of the experimental data, and decided to use the nonparametric test according to the results. We used the SPSS18.0 to rank the transformed data, and used the Kruskal-Wallis test for the independent samples, and the Mann-Whitney U test for two samples.Results: In comparison with the group A, the expression of m TOR/p-S6, insulin positive area and β cell number per islet increased(P<0.01), and the serum insulin levels increased(P<0.05)in the group B. The expression of p-S6 and the β cell number per islet decreased(P<0.01) and the insulin positive area decreased(P<0.05)in the group C. In comparison with the group B, the insulin positive area decreased(P < 0.05) as well as the other indexes(P < 0.01) in the group C.Conclusion: CIH activated the m TOR pathway which induced an increase in the number of pancreatic islet β cells. Rapamycin could inhibit the activation of m TOR pathway and decrease the expression of the m TOR pathway related proteins and the β cell number in rats under CIH.