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Prevention of Hyperglycemic Signal Pathways in Metabolic Syndrome Carotid Artery of Rats

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Abstract

Obesity is the major risk factor for metabolic syndrome and atherosclerotic cardiocerebrovascular diseases and induces insulin resistance characterized by a dysfunction of insulin to activate insulin receptor /insulin receptor substrate 1(IRS-1)/phosphoinositide 3-kinase (PI3K)/Akt pathway. Zucker fatty rats (8 weeks) were treated with vehicle (0.5 % methyl cellulose in physiological saline, p.o.), amlodipine (3 mg/kg/day, p.o.), atorvastatin (10 mg/kg/day, p.o.), or the combination of amlodipine plus atorvastatin (3 + 10 mg/kg/day, p.o.) for 28 days, and anti-insulin-like growth factor 1 (IGF-1)/IRS-1/PI3K/Akt pathways were evaluated. Our present immunohistochemical study first demonstrated that a combination of amlodipine plus atorvastatin treatment prevented an arteriosclerotic process compared to the single treatment with amlodipine or atorvastatin with strong recoveries of pTyr IRS-1, pPI3K, and pAkt expressions and with remarkable restraints of IGF-1 and pSer IRS-1. As a result, combination therapy with amlodipine plus atorvastatin showed a strong synergistic effect to prevent atherosclerotic processes. The present study newly suggests a synergistic benefit of combination therapy with amlodipine plus atorvastatin for strong prevention of atherosclerotic processes, which could reduce the clinical risk of cerebrovascular events for obesity patients.

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Abbreviations

IGF-1:

Insulin-like growth factors 1

IRS-1:

Insulin receptor substrate 1

PI3K:

Phosphoinositide 3-kinase

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Acknowledgments

This study was supported in part by Grant-in-Aid for Scientific Research (B) 21390267 and the Ministry of Education, Science, Culture and Sports of Japan; by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases (Nakano I); and by grants (Mizusawa H, Nishizawa M, Sasaki H, and Sobue G) from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Neurology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikatacho, Okayama, 700-8558, Japan

    Hiromi Kawai, Fengfeng Tian, Tomoko Kurata, Kentaro Deguchi, Toru Yamashita, Yoshio Omote, Syoichiro Kono & Koji Abe

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  1. Hiromi Kawai
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  2. Fengfeng Tian
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Correspondence to Koji Abe.

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Kawai, H., Tian, F., Kurata, T. et al. Prevention of Hyperglycemic Signal Pathways in Metabolic Syndrome Carotid Artery of Rats. Transl. Stroke Res. 3, 466–472 (2012). https://doi.org/10.1007/s12975-012-0205-6

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  • DOI: https://doi.org/10.1007/s12975-012-0205-6

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