Guang-yu Liu1, Zhen-mei An. 1. Department of Endocrinology, West China Hospital, Sichuan University, Chengdu 610041, China.
Abstract
OBJECTIVE: To observe the effect of rosiglitazone sodium on survival of pancreatic beta-cell of STZ induced diabetic rats and explore its impact on JNK pathway. METHODS: Total 34 SD rats were randomly assigned into three groups: control group (6 rats), diabetic group (14 rats) and rosiglitazone sodium-treated diabetic group (14 rats). STZ was administered intraperitoneally at a dose of 50 mg/kg for the latter two groups, then rosiglitazone sodium (4 mg/kg x d) was force-fed to diabetic rats in rosiglitazone sodium-treated group. Ten (10) weeks later, all the animals were subjected to oral glucose tolerance test to evaluate the function of pancreatic islet, then the rats were sacrified to obtain pancreatic tissue for histopathological study. The expression levels of INS, Caspase-3 and P-JNK in pancreatic islet were measured by immunohistochemistry and the apoptosis rates of beta-cells were measured by TUNEL. RESULTS: 1) Compared with non-treated diabetic group, the levels of blood glucose (BG) in rosiglitazone sodium-treated group were lower at 0 h, 0.5 h, 1 h, 2 h in OGTT, which were (22.8 +/- 5.79) mmol/L vs (9.9 +/- 6.99) mmol/L, (29.33 +/- 3.29) mmol/L vs (25.63 +/- 4.56) mmol/L, (31.90 +/- 2.56) mmol/L vs (26.07 +/- 4.75) mmol/L, (25.08 +/- 3.53) mmol/L vs (21.47 +/- 6.64) mmol/L respectively (P<0.05). The levels of INS at 0 h and 2 h were [(17.49 +/- 4.59) microU/L (non-treated)] vs [(23.59 +/- 4.59) microU/L (treated)] and [(20.24 +/- 3.32) microU/L (non-treated)] vs [(30.98 +/- 9.15) microU/L (treated)] respectively, which showed INS of rosiglitazone sodium-treated group were higher, but without statistical significance (P=0.056). The function of pancreatic islet in rosiglitazone sodium-treated group seemed better than that of non-treated group. 2) Compared with non-treated diabetic group, the margin of pancreatic islets in rosiglitazone sodium-treated group were clearer, beta-cells were more regularly arranged, chromatin were more abundant. 3) The levels of INS expression in islets were significantly higher in rosiglitazone sodium-treated group than that of non-treated diabetic group (P<0.05). 4) TUNEL assay showed that the apoptosis rate (%) of beta-cells in rosiglitazone sodium-treated group was smaller than that of non-treated group (6.52 +/- 0.77 vs 10.33 +/- 1.07), and the difference was statistical significance (P<0.05). At the same time, the expression of caspase-3 was significantly deceased in rosiglitazone sodium-treated group compared with diabetic control group (P<0.05). 5) A lower level of P-JNK expression in pancreatic islet was observed in rosiglitazone sodium-treated group than that in non-treated group (P<0.05). CONCLUSION: Rosiglitazone sodium can reduce the apoptosis rates of beta-cells, improve the function of pancreatic islet of STZ induced diabetic rats and decrease blood glucose. The anti-apoptosis effect of Rosiglitazone sodium on beta-cell may be induced through JNK pathway.
OBJECTIVE: To observe the effect of rosiglitazone sodium on survival of pancreatic beta-cell of STZ induced diabeticrats and explore its impact on JNK pathway. METHODS: Total 34 SD rats were randomly assigned into three groups: control group (6 rats), diabetic group (14 rats) and rosiglitazone sodium-treated diabetic group (14 rats). STZ was administered intraperitoneally at a dose of 50 mg/kg for the latter two groups, then rosiglitazone sodium (4 mg/kg x d) was force-fed to diabeticrats in rosiglitazone sodium-treated group. Ten (10) weeks later, all the animals were subjected to oral glucose tolerance test to evaluate the function of pancreatic islet, then the rats were sacrified to obtain pancreatic tissue for histopathological study. The expression levels of INS, Caspase-3 and P-JNK in pancreatic islet were measured by immunohistochemistry and the apoptosis rates of beta-cells were measured by TUNEL. RESULTS: 1) Compared with non-treated diabetic group, the levels of blood glucose (BG) in rosiglitazone sodium-treated group were lower at 0 h, 0.5 h, 1 h, 2 h in OGTT, which were (22.8 +/- 5.79) mmol/L vs (9.9 +/- 6.99) mmol/L, (29.33 +/- 3.29) mmol/L vs (25.63 +/- 4.56) mmol/L, (31.90 +/- 2.56) mmol/L vs (26.07 +/- 4.75) mmol/L, (25.08 +/- 3.53) mmol/L vs (21.47 +/- 6.64) mmol/L respectively (P<0.05). The levels of INS at 0 h and 2 h were [(17.49 +/- 4.59) microU/L (non-treated)] vs [(23.59 +/- 4.59) microU/L (treated)] and [(20.24 +/- 3.32) microU/L (non-treated)] vs [(30.98 +/- 9.15) microU/L (treated)] respectively, which showed INS of rosiglitazone sodium-treated group were higher, but without statistical significance (P=0.056). The function of pancreatic islet in rosiglitazone sodium-treated group seemed better than that of non-treated group. 2) Compared with non-treated diabetic group, the margin of pancreatic islets in rosiglitazone sodium-treated group were clearer, beta-cells were more regularly arranged, chromatin were more abundant. 3) The levels of INS expression in islets were significantly higher in rosiglitazone sodium-treated group than that of non-treated diabetic group (P<0.05). 4) TUNEL assay showed that the apoptosis rate (%) of beta-cells in rosiglitazone sodium-treated group was smaller than that of non-treated group (6.52 +/- 0.77 vs 10.33 +/- 1.07), and the difference was statistical significance (P<0.05). At the same time, the expression of caspase-3 was significantly deceased in rosiglitazone sodium-treated group compared with diabetic control group (P<0.05). 5) A lower level of P-JNK expression in pancreatic islet was observed in rosiglitazone sodium-treated group than that in non-treated group (P<0.05). CONCLUSION:Rosiglitazone sodium can reduce the apoptosis rates of beta-cells, improve the function of pancreatic islet of STZ induced diabeticrats and decrease blood glucose. The anti-apoptosis effect of Rosiglitazone sodium on beta-cell may be induced through JNK pathway.