Os efeitos da inibição aguda da expressão do substrato-1 do receptor de insulina (IRS-1) sobre a secreção e ação da insulina em ratos wistar

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

Insulin receptor substrate-1 (IRS-1) has an important role as an early intermediary between the insulin and IGF-1 receptors and downstream molecules that participate in the insulin and IGF-1 signal transduction. We employed an antisense oligonucleotide (IRS-1 AS) to inhibit whole-body expression of IRS-1 in vivo and evaluate the consequences of short-term inhibition of IRS-1 in Wistar rats. Four days treatment with IRS-1 AS reduced the expression of IRS-1 by 80, 75 and 65% (P<0.05) in liver, skeletal muscle, and adipose tissue, respectively. This was accompanied by a 40% (P<0.05) reduction in the constant of glucose decay during an insulin tolerance test, a 78% (P<0.05) reduction in glucose consumption during a hyperinsulinemic-euglicemic clamp, and a 90% (P<0.05) increase in basal plasma insulin levels. The metabolic effects produced by IRS-1AS were accompanied by a significant reduction in insulin-induced [Ser473] Akt phosphorylation in liver (85%, P<0.05), skeletal muscle (40%, P<0.05), and adipose tissue (85%, P<0.05) and a significant reduction in insulin-induced tyrosine phosphorylation of ERK in liver (20%, P<0.05) and skeletal muscle (30%, P<0.05). However, insulin-induced tyrosine phosphorylation of ERK was significantly increased (60%, P<0.05) in adipose tissue of IRS-1 AS treated rats. Moreover, in rats treated with IRS-1 AS for 8 days, a 100% increase (P<0.05) in relative epididymal fat weight and a 120% (P<0.05) increase in nuclear expresssion of peroxisome proliferator-activated receptor-? were observed. Thus, acute inhibition of IRS-1 expression in rats leads to insulin resistance accompanied by activation of a gowth-related pathway exclusively in white adipose tissue

ASSUNTO(S)

obesidade tecido adiposo resistencia a insulina diabetes

ACESSO AO ARTIGO

Documentos Relacionados