Regulação da transmissão do sinal insulinico em pele intacta e em cicatrização de ratos controles e diabeticos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

Insulin is an important regulator of growth and initiates its action by binding to its receptor that undergoes tyrosyl autophosphorylation and further enhances its tyrosine kinase activity towards other intermediate molecules, including insulin receptor substrate-1 (IRS-l), IRS-2 and Shc. IRSs proteins can dock various SH2-containing signaling proteins, such as the 85 kDa subunit of phosphatidylinositol 3-kinase (pI 3-kinase) and Grb2. The serine-threonine kinase Akt is activated downstream to PI 3-kinase. Shc protein has been shown to directly induce the association with Grb2 and downstream the activation of the mitogen-activated protein kinase (MAPK). In the present study we investigated insulin signal transduction pathways in skin of intact rats by immunoprecipitation and immunoblotting with specific antibodies, and also by immunohistochemistry with anti-insulin receptor antibody. Our results showed that skin fragments clearly demonstrated the presence of insulin receptor (IR) in cell bodies of the epidermis and hair follicles and some faint staining was also detected in fibroblasts of the dermis. It was also observed that acute stimulation with insulin can induce tyrosyl phosphorylation of IR and that the IRSs and Shc proteins serve as signaling molecules for insulin in skin of rats and that insulin is able to induce association of IRS-1/PI 3-kinase and Shc/Grb2 in this tissue, as well as phosphorylation of MAPK and Akt, demonstrating that proteins involved in early steps of insulin action are expressed in skin of intact rats and are quickly activated afier insulin stimulation. Wound healing is impaired in diabetes mellitus. However the pathogenesis ofthis process is not known and may involve abnormalities in insulin signaling. The other purpose of this study was to investigate the regulation of these proteins in wound healing skin of normal and diabetic rats. Our results showed that insulin induced tyrosyl phosphorylation and tissue expression ofIR, IRS-l, IRS-2, SHC, MAPK and Akt, are increased in the wound healing tissue compared to intact skin and decreased in wounded skin of diabetic rats when compared to wounded skin of normal rats. Insulin signal transduction is increased in repair tissue in skin and it is possible that abnormal insulin signaling, as demonstrated in skin of diabetic rats, could affect skin function

ASSUNTO(S)

ferimentos e lesões insulina - secreção diabetes mellitus diabetes

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