Chymase inhibition provides pancreatic islet protection in hamsters with streptozotocin-induced diabetes.
Angiotensin II 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 1 week. A significant increase in blood glucose level was observed at 1 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.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College, Daigaku-machi 2-7, Takatsuki City, Osaka, Japan. pha010@art.osaka-med.ac.jp
Jin
Denan
D
Ohzu
Mariko
M
Tanaka
Kazuhiko
K
Miyazaki
Mizuo
M
D000804:Angiotensin II / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D053818:Chymases / Q000037:antagonists & inhibitors*; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D013311:Streptozocin; D013449:Sulfonamides / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors
D001786:Blood Glucose; D013449:Sulfonamides; C524344:TY 51469; D013876:Thiophenes; D000804:Angiotensin II; D008315:Malondialdehyde; D013311:Streptozocin; D007703:Peptidyl-Dipeptidase A; D053818:Chymases