title: Excess aldosterone-induced changes in insulin signaling molecules and glucose oxidation in gastrocnemius muscle of adult male rat.
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.
authors.affiliation: Department of Endocrinology, Dr.ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Sekkizhar Campus, Taramani, Chennai 600113, India.
authors.forename: Jayaraman
authors.initials: J
authors.lastname: Selvaraj
authors.forename: Sampath
authors.initials: S
authors.lastname: Sathish
authors.forename: Chinnaiyan
authors.initials: C
authors.lastname: Mayilvanan
authors.forename: Karundevi
authors.initials: K
authors.lastname: Balasubramanian
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D001786:Blood Glucose; D000081247:CSK Tyrosine-Protein Kinase; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D020690:GTPase-Activating Proteins / Q000378:metabolism; D018149:Glucose Intolerance / Q000097:blood; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013739:Testosterone / Q000097:blood; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C000605257:Arrb2 protein, rat; D019390:Arrestins; D001786:Blood Glucose; D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C495694:Slc2a4 protein, rat; C533101:TBC1D4 protein, rat; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D013739:Testosterone; D000450:Aldosterone; D006003:Glycogen; D011972:Receptor, Insulin; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt