title: Potential role of growth hormone in impairment of insulin signaling in skeletal muscle, adipose tissue, and liver of rats chronically treated with arginine.
abstract: We have shown that rats chronically treated with Arginine (Arg), although normoglycemic, exhibit hyperinsulinemia and decreased blood glucose disappearance rate after an insulin challenge. Attempting to investigate the processes underlying these alterations, male Wistar rats were treated with Arg (35 mg/d), in drinking water, for 4 wk. Rats were then acutely stimulated with insulin, and the soleus and extensorum digitalis longus muscles, white adipose tissue (WAT), and liver were excised for total and/or phosphorylated insulin receptor (IR), IR substrate 1/2, Akt, Janus kinase 2, signal transducer and activator of transcription (STAT) 1/3/5, and p85alpha/55alpha determination. Muscles and WAT were also used for plasma membrane (PM) and microsome evaluation of glucose transporter (GLUT) 4 content. Pituitary GH mRNA, GH, and liver IGF-I mRNA expression were estimated. It was shown that Arg treatment: 1) did not affect phosphotyrosine-IR, whereas it decreased phosphotyrosine-IR substrate 1/2 and phosphoserine-Akt content in all tissues studied, indicating that insulin signaling is impaired at post-receptor level; 2) decreased PM GLUT4 content in both muscles and WAT; 3) increased the pituitary GH mRNA, GH, and liver IGF-I mRNA expression, the levels of phosphotyrosine-STAT5 in both muscles, phosphotyrosine-Janus kinase 2 in extensorum digitalis longus, phosphotyrosine-STAT3 in liver, and WAT as well as total p85alpha in soleus, indicating that GH signaling is enhanced in these tissues; and 4) increased p55alpha total content in muscles, WAT, and liver. The present findings provide the molecular mechanisms by which insulin resistance and, by extension, reduced GLUT4 content in PM of muscles and WAT take place after chronic administration of Arg, and further suggest a putative role for GH in its genesis, considering its diabetogenic effect.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, São Paulo, Brazil.
authors.forename: Thais
authors.initials: T
authors.lastname: de Castro Barbosa
authors.forename: José Edgar Nicoletti
authors.initials: JE
authors.lastname: de Carvalho
authors.forename: Leonice Lourenço
authors.initials: LL
authors.lastname: Poyares
authors.forename: Silvana
authors.initials: S
authors.lastname: Bordin
authors.forename: Ubiratan Fabres
authors.initials: UF
authors.lastname: Machado
authors.forename: Maria Tereza
authors.initials: MT
authors.lastname: Nunes
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013997:Time Factors
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; C495694:Slc2a4 protein, rat; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D001120:Arginine; D011972:Receptor, Insulin; D051058:Oncogene Protein v-akt