Ramipril treatment suppresses islet fibrosis in Otsuka Long-Evans Tokushima fatty rats.
We evaluated whether ramipril, one of long-acting ACEIs, has a direct effect on pancreas islets in animal model of type 2 diabetes. OLETF rats were treated with ramipril for 24 weeks. We assessed the body weight, glucose tolerance, and the amount of islet fibrosis. RT-PCR and Western blot analysis of transforming growth factor-beta with its downstream signals were performed from the pancreas. Ramipril treatment remarkably reduced weight gain and the area under the curve of glucose. Islet fibrosis and the expression of TGF-beta with its downstream signal molecules were significantly reduced in the pancreas of ramipril-treated group than in control and paired-feeding group. These beneficial effects of ramipril might be related to the downregulation of TGF-beta and its downstream signals in OLETF rats. To our knowledge, this is the first report suggesting the potential effect of ramipril on the prevention of islet destruction by fibrosis in the animal model of type 2 diabetes mellitus.
Ko
Seung-Hyun
SH
Division of Endocrinology and Metabolism, Department of Internal medicine, Immunology and Cell Biology Core Laboratory, The Catholic University of Korea, Seoul, Republic of Korea.
Kwon
Hyuk-Sang
HS
Kim
Sung-Rae
SR
Moon
Sung-Dae
SD
Ahn
Yu-Bae
YB
Song
Ki-Ho
KH
Son
Hyun-Sik
HS
Cha
Bong-Yun
BY
Lee
Kwang-Woo
KW
Son
Ho-Young
HY
Kang
Sung-Koo
SK
Park
Chung-Gyu
CG
Lee
In-Kyu
IK
Yoon
Kun-Ho
KH
D000199:Actins / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D017257:Ramipril / Q000627:therapeutic use*; D051381:Rats; D020334:Rats, Inbred OLETF; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D000199:Actins; D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D017257:Ramipril