@article{APS4203,
author = {Jia-qing Shao and Noseki Iwashita and Hong Du and Yang-tian Wang and Yan-yan Wang and Ming Zhao and Jian Wang and Hirotaka Watada and Ryuzo Kawamori},
title = {Angiotensin II receptor blocker provides pancreatic β-cell protection independent of blood pressure lowering in diabetic db/db mice},
journal = {Acta Pharmacologica Sinica},
volume = {28},
number = {2},
year = {2016},
keywords = {},
abstract = {Aim: Several epidemiological studies have suggested that treatment with angiotensin II type 1 receptor blocker provided a risk reduction of developing type 2 diabetes. The aim of this study was to investigate whether and how chronic candesartan treatment can attenuate the deleterious influence of the hyperactive local intra-islet renin-angiotensin system in the diabetes state.
Methods: Eightweek-old db/db mice were randomized to candesartan 1 mg/kg, candesartan 10 mg/kg, manidipine 10 mg/kg, or placebo via gavage for 6 weeks. Their age-matched nondiabetic littermates db/m mice were treated with placebo and acted as nondiabetic controls. After 6 weeks’ treatment, an intraperitoneal glucose tolerance test, immunohistochemical staining of oxidative stress markers, insulin, CD31, azan staining and an electron microscopy observation were performed.
Results: Chronic candesartan treatment provided an improvement of glucose tolerance, and greatly rescued islet β-cell mass. Candesartan treatment also notably decreased staining intensity of oxidative stress markers, as well as attenuating intra-islet fibrosis and improving blood supply in the islet. In the electron microscopy observation, candesartan-treated animals exhibited improved granulation and less remarkable endoplasmic reticulum and Golgi bodies; furthermore, candesartan treatment greatly relieved the swelling of mitochondria to nearly normal. Both the benefits of reducing oxidative stress and ultrastructure protection were in a dose-dependent and blood pressure-independent manner.
Conclusion: After diabetes was initiated, candesartan treatment could not reverse the state of diabetes, but it effectively improved glucose tolerance and protected β-cell function by attenuating oxidative stress, islet fibrosis, sparsity of blood supply and ultrastructure disruption in a dose-dependent and blood pressure-independent manner.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4203}
}