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

• Published in: Molecular and cellular biochemistry 2013-01, Vol.372 (1-2), p.113-126
• Main Authors: Selvaraj, Jayaraman, Sathish, Sampath, Mayilvanan, Chinnaiyan, Balasubramanian, Karundevi
• Format: Article
• Language: English
• Subjects: Aldosterone; Aldosterone - blood; Aldosterone - pharmacology; Aldosterone - physiology; Animals; Arrestins - metabolism; beta-Arrestin 2; beta-Arrestins; Biochemistry; Biomedical and Life Sciences; Blood Glucose; Body weight; Cardiology; Corticosteroids; Dextrose; Diabetes; Diabetes Mellitus, Type 2 - blood; Dosage and administration; Ethanol; Glucose; Glucose Intolerance - blood; Glucose metabolism; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Glycogen - metabolism; GTPase-Activating Proteins - metabolism; Insulin; Insulin - blood; Insulin - physiology; Insulin Receptor Substrate Proteins - genetics; Insulin Receptor Substrate Proteins - metabolism; Insulin resistance; Life Sciences; Lipid Peroxidation; Male; Medical Biochemistry; Muscle, Skeletal - metabolism; Muscles; Oncology; Oxidation; Oxidation-Reduction; Oxidation-reduction reaction; Phosphorylation; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Wistar; Reactive Oxygen Species - metabolism; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Signal Transduction; Signaling; src-Family Kinases - metabolism; Steroids; Testosterone; Testosterone - blood
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-012-1452-2

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.