Estudo da sinalização da insulina nos tecidos muscular e adiposo de ratos submetidos à desnutrição materna no início da lactação

• Autor(a) principal: Souza , Érica Patrícia Garcia de
• Data de Publicação: 2005
• Outros Autores: [e-mail]
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/17724
• topic: Desnutrição; Insulina - Sinalização; Músculos; Tecido adiposo; Lactação; Insulin; Insulin resistance; Undernutrition; Insulin signaling; CIENCIAS DA SAUDE::NUTRICAO

Early postnatal undernutrition hás been associated with the long-term effects on glucose homeostasis in adulthood. To elucidate the molecular mechanism by which undernutrition during early life leads to changes in insulin sensitivity, we investigated the insulin signaling in skeletal muscle and in adipose tissue of rats. Offspring of dams fed with either protein-free or normal diets during the first 10 days of lactation were studied from lactation period until adulthood. Early maternal undernutrition impaired secretion of insulin but maintained normal blood glucose levels until adulthood. Insulin receptor (IR) activation after insulin stimulation was decreased during the period of protein restriction. In addition, glucose uptake, insulin receptor substrate 1 (IRS – 1) phosphorylation and glucose transporter 4 (GLUT – 4) translocation in muscle were reduced in response to insulin during suckling. In contrast, non- or insulin-stimulated glucose uptake and GLUT – 4 translocation were found significantly increased in muscle of adult offspring. The basal association of phosphatidylinositol 3 – Kinase (PI3 – Kinase) with IRS – 1 was increased and was highly stimulated by insulin in muscle from adult rats. Finally, adipocytes isolated of undernourished adult rats presented reduced tyrosine phosphorylation of IR and IRS – 1 after insulin stimulation, but this inhibition was compensated by upregulation of IRS- 2 and PI3 – Kinase. The pAkt levels and GLUT – 4 translocation was increased in the basal state. Finally, we observed alterations in the actin cytoskeleton and an increased glucose uptake in this cells. Our findings suggest that early postnatal undernutrition impairs insulin sensitivity in adulthood, which appears to be directly related to changes in critical steps of insulin signaling in periferic tissues, required for glucose metabolism.