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Akt activation by insulin treatment attenuates cachexia in Walker-256 tumor-bearing rats.
de Fatima Silva, Flaviane; de Morais, Hely; Ortiz Silva, Milene; da Silva, Francemilson Goulart; Vianna Croffi, Rafael; Serrano-Nascimento, Caroline; Rodrigues Graciano, Maria Fernanda; Rafael Carpinelli, Angelo; Barbosa Bazotte, Roberto; de Souza, Helenir Medri.
Afiliação
  • de Fatima Silva F; Department of Physiological Sciences, State University of Londrina, Londrina, Parana, Brazil.
  • de Morais H; Department of Physiological Sciences, State University of Londrina, Londrina, Parana, Brazil.
  • Ortiz Silva M; Department of Physiological Sciences, State University of Londrina, Londrina, Parana, Brazil.
  • da Silva FG; Department of Physiology and Biophysics, University of São Paulo, São Paulo, Parana, Brazil.
  • Vianna Croffi R; Department of Physiology and Biophysics, University of São Paulo, São Paulo, Parana, Brazil.
  • Serrano-Nascimento C; Department of Physiology and Biophysics, University of São Paulo, São Paulo, Parana, Brazil.
  • Rodrigues Graciano MF; Department of Physiological Sciences, State University of Londrina, Londrina, Parana, Brazil.
  • Rafael Carpinelli A; Department of Physiology and Biophysics, University of São Paulo, São Paulo, Parana, Brazil.
  • Barbosa Bazotte R; Department of Pharmacology and Therapeutics, State University of Maringá, Maringa, Parana, Brazil.
  • de Souza HM; Department of Physiological Sciences, State University of Londrina, Londrina, Parana, Brazil.
J Cell Biochem ; 121(11): 4558-4568, 2020 11.
Article em En | MEDLINE | ID: mdl-32056265
Cancer-bearing often exhibits hypoinsulinemia, insulin (INS) resistance and glutamine depletion associated with cachexia. However, INS and glutamine effects on cachexia metabolic abnormalities, particularly on tumor-affected proteins related to INS resistance, are poorly known. The main purpose of this study was to investigate the effects of INS and glutamine dipeptide (GDP) treatments on phospho-protein kinase B (p-Akt), and phospho-hormone sensitive lipase (p-HSL) in Walker-256 tumor-bearing rats. INS (NPH, 40 UI/kg, subcutaneous), GDP (1.5 g/kg, oral), INS+GDP or vehicle (control rats) were administered for 13 days, once a day, starting at the day of inoculation of tumor cells. The experiments were performed 4 hours after the last treatment to evaluate acute effects of INS and GDP, besides the chronic effects. INS and/or INS+GDP treatments, which markedly increased the insulinemia, increased the p-Akt: total Akt ratio and prevented the increased p-HSLSer552 : total HSL ratio in the retroperitoneal fat of tumor-bearing rats, without changing the INS resistance and increased expression of factor tumor necrosis-α (TNF-α) in this tissue. INS and INS+GDP also increased the p-Akt: total Akt ratio, whereas GDP and INS+GDP increased the GLUT4 glucose transporter gene expression, in the gastrocnemius muscle of the tumor-bearing rats. Accordingly, treatments with INS and INS+GDP markedly reduced glycemia, increased retroperitoneal fat and attenuated the body mass loss of tumor-bearing rats. In conclusion, hyperinsulinemia induced by high-dose INS treatments increased Akt phosphorylation and prevented increased p-HSLSer552 : total HSL ratio, overlapping INS resistance. These effects are consistent with increased fat mass gain and weight loss (cachexia) attenuation of tumor-bearing rats, evidencing that Akt activation is a potential strategy to prevent loss of fat mass in cancer cachexia.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Caquexia / Carcinoma 256 de Walker / Proteínas Proto-Oncogênicas c-akt / Glutamina / Hipoglicemiantes / Insulina Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: J Cell Biochem Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Caquexia / Carcinoma 256 de Walker / Proteínas Proto-Oncogênicas c-akt / Glutamina / Hipoglicemiantes / Insulina Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: J Cell Biochem Ano de publicação: 2020 Tipo de documento: Article