| Autor: |
Jia-qing Shao, Iwashita, Noseki, Hong Du, Yang-tian Wang, Yan-yan Wang, Ming Zhao, Jian Wang, Watada, Hirotaka, Kawamori, Ryuzo |
| Předmět: |
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| Zdroj: |
Acta Pharmacologica Sinica; Feb2007, Vol. 28 Issue 2, p246-257, 12p, 7 Color Photographs, 2 Black and White Photographs, 1 Diagram, 1 Chart, 11 Graphs |
| Abstrakt: |
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: Eight-week-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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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