Chymase Inhibition Provides Pancreatic Islet Protection in Hamsters With Streptozotocin-Induced Diabetes
Chymase Inhibition Provides Pancreatic Islet Protection in Hamsters With Streptozotocin-Induced Diabetes
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DOI：
10.1254/jphs.09115fp
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发表时间：
2009-08-01
影响因子：
3.5
通讯作者：
Miyazaki, Mizuo
中科院分区：
文献类型：
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作者：
Takai, Shinji;Jin, Denan;Miyazaki, Mizuo
血管紧张素 R 可能参与胰腺破坏，但食糜酶的参与尚不清楚。在本研究中，我们检查了食糜酶是否与链脲佐菌素 (STZ) 诱导的糖尿病仓鼠的胰腺紊乱有关。给仓鼠注射链脲佐菌素（60 mg/kg），未注射的仓鼠作为对照。为了研究食糜酶抑制剂 TY-51469（每天 30 mg/kg）的效果，STZ 组的仓鼠从注射 STZ 后 2 周开始施用 TY-51469 或安慰剂，持续 I 周。注射 STZ 后第 1 周观察到血糖水平显着升高。 2周时这一情况得以维持，3周时观察到进一步显着增加。直到注射 STZ 后 2 周，所有血管紧张素 II 相关酶活性均未变化，但在 3 周时，胰糜酶和总血管紧张素 II 形成活性显着增加，但血管紧张素转换酶活性未显着增加。 TY-51469 显着降低血糖水平，同时降低食糜酶和总血管紧张素 II 形成活性以及丙二醛水平。此外，TY-51469 组的胰岛数量明显多于安慰剂组。总之，食糜酶抑制可能可以防止胰岛解体。
Angiotensin R may be involved in pancreatic disorganization, but the involvement of chymase has been unclear. In the present study, we examined whether chymase is involved in pancreatic disorganization in hamsters with streptozotocin (STZ)-induced diabetes. Hamsters were injected with streptozotocin (60 mg/kg), and non-injected hamsters served as controls. To investigate the effect of a chymase inhibitor, TY-51469 (30 mg/kg per day), hamsters in the STZ group were administered TY-51469 or placebo from 2 weeks after STZ injection, for I week. A significant increase in blood glucose level was observed at I week after STZ injection. This was maintained at 2 weeks, and a further significant increase was observed at 3 weeks. Until 2 weeks after STZ injection, all angiotensin II-related enzyme activities were unchanged, but at 3 weeks pancreatic chymase and total angiotensin II-forming activities, but not angiotensin-converting enzyme activity, were significantly increased. TY-51469 significantly attenuated blood glucose level along with reductions of chymase and total angiotensin II-forming activities and malondialdehyde level. Furthermore, there were significantly more pancreatic islets in the TY-51469 group than in the placebo group. In conclusion, chymase inhibition might protect against pancreatic islet disorganization.