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Excess aldosterone-induced changes in insulin signaling molecules and glucose oxidation in gastrocnemius muscle of adult male rat

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Abstract

Emerging evidences demonstrate that excess aldosterone and insulin interact at target tissues. It has been shown that increased levels of aldosterone contribute to the development of insulin resistance and thus act as a risk factor for the development of type-2 diabetes mellitus. However, the molecular mechanisms involved in this scenario are yet to be identified. This study was designed to assess the dose-dependent effects of aldosterone on insulin signal transduction and glucose oxidation in the skeletal muscle (gastrocnemius) of adult male rat. Healthy adult male albino rats of Wistar strain (Rattus norvegicus) weighing 180–200 g were used in this study. Rats were divided into four groups. Group I: control (treated with 1 % ethanol only), group II: aldosterone treated (10 μg /kg body weight, twice daily for 15 days), group III: aldosterone treated (20 μg /kg body weight, twice daily for 15 days), and group IV: aldosterone treated (40 μg/kg body weight, twice daily for 15 days). Excess aldosterone caused glucose intolerance in a dose-dependent manner. Serum insulin and aldosterone were significantly increased, whereas serum testosterone was decreased. Aldosterone treatment impaired the rate of glucose uptake, oxidation, and insulin signal transduction in the gastrocnemius muscle through defective expression of IR, IRS-1, Akt, AS160, and GLUT4 genes. Phosphorylation of IRS-1, β-arrestin-2, and Akt was also reduced in a dose-dependent manner. Excess aldosterone results in glucose intolerance as a result of impaired insulin signal transduction leading to decreased glucose uptake and oxidation in skeletal muscle. In addition to this, it is inferred that excess aldosterone may act as one of the causative factors for the onset of insulin resistance and thus increased incidence of type-2 diabetes.

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Acknowledgments

University Grants Commission Special Assistance Programme (UGC-SAP), Department of Science and Technology (DST)–FIST Programme, UGC-Research Fellowship in Science for Meritorious Students (UGC-RFSMS) and Council of Scientific and Industrial Research (CSIR) are gratefully acknowledged for the financial support.

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Authors and Affiliations

  1. Department of Endocrinology, Dr.ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Sekkizhar Campus, Taramani, Chennai, 600113, India

    Jayaraman Selvaraj, Sampath Sathish, Chinnaiyan Mayilvanan & Karundevi Balasubramanian

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  1. Jayaraman Selvaraj
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  2. Sampath Sathish
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Correspondence to Karundevi Balasubramanian.

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Selvaraj, J., Sathish, S., Mayilvanan, C. et al. Excess aldosterone-induced changes in insulin signaling molecules and glucose oxidation in gastrocnemius muscle of adult male rat. Mol Cell Biochem 372, 113–126 (2013). https://doi.org/10.1007/s11010-012-1452-2

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