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Olmesartan and telmisartan comparably preserve pancreatic beta-cell mass with reduction of oxidative stress in db/db mice

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Abstract

Several clinical studies have provided evidence that blockade of the renin–angiotensin system (RAS) prevents onset of type 2 diabetes. In mice models of type 2 diabetes, some angiotensin II type 1 receptor blockers (ARBs) reportedly protect against reduction of beta-cell mass. Although several ARBs are commercially available, the effect of these drugs on beta-cell mass has not been compared directly. The purpose of this study was to compare the protective effects on beta cell mass of olmesartan, an ARB with strong binding capacity to the angiotensin II type 1 receptor, and telmisartan, an ARB with partial peroxisome proliferator-activated receptor-γ (PPARγ) activity. Eight-week-old female db/db mice were treated with olmesartan medoxomil (3.0 mg/kg body weight/day), telmisartan (1.5 mg/kg body weight/day), or placebo for 6 weeks. This was followed by examination of glucose tolerance, insulin sensitivity, and islet morphology in each group. Random glucose level after treatment with the two ARBs was slightly, but significantly, lower than in the placebo group whereas glucose tolerance and insulin sensitivity were similar among the three groups. Beta-cell mass was higher and staining intensities for NAD(P)H oxidase components and markers of oxidative stress were lower in islets of the olmesartan and telmisartan-treated groups than in those of the placebo group. Our results reveal that olmesartan and telmisartan had comparable effects on reduction of beta-cell mass in db/db mice via their antioxidant effects.

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Abbreviations

AT1(2)R:

Angiotensin II type 1 (2) receptor

ARBs:

Angiotensin II (Ang II) receptor blockers

IPGTT:

Intraperitoneal glucose tolerance test

ITT:

Insulin tolerance test

RAS:

Renin–angiotensin system

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Acknowledgments

We thank Mrs Naoko Daimaru for excellent technical assistance.

Conflict of interest

H.W. has received lecture fees from Daiichi Sankyo, Takeda, MSD, Sanofi–Aventis, Ono, Novartis, Astellas, Dainippon Sumitomo, Tanabe Mitsubishi, Novo Nordisk, and Sanwakagaku, and research funding from Sanofi–Aventis, Novo Nordisk, Novartis, AstraZeneca, Sanwakagaku, Ono, MSD, Boehringer Ingelheim, Kissei, Takeda, and Daiichi Sankyo. Y.F. received lecture fees from Novartis and Eli Lilly.

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Authors and Affiliations

  1. Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Nayumi Shigihara, Toyoyoshi Uchida, Yukiko Toyofuku, Motoyuki Tamaki, Yoshio Fujitani & Hirotaka Watada

  2. Department of Obstetrics and Gynecology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Takashi Yorifuji & Hirotaka Watada

  3. Center for Beta Cell Biology and Regeneration, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Yoshio Fujitani & Hirotaka Watada

  4. Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Hirotaka Watada

  5. Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Hirotaka Watada

Authors
  1. Nayumi Shigihara
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  2. Toyoyoshi Uchida
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  3. Takashi Yorifuji
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  4. Yukiko Toyofuku
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  5. Motoyuki Tamaki
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  6. Yoshio Fujitani
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  7. Hirotaka Watada
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Correspondence to Toyoyoshi Uchida.

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Shigihara, N., Uchida, T., Yorifuji, T. et al. Olmesartan and telmisartan comparably preserve pancreatic beta-cell mass with reduction of oxidative stress in db/db mice. Diabetol Int 5, 62–68 (2014). https://doi.org/10.1007/s13340-013-0135-x

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  • DOI: https://doi.org/10.1007/s13340-013-0135-x

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