Regulation of IRS-2 tyrosine phosphorylation in fasting and diabetes

• Published in: Molecular and cellular endocrinology Vol. 183; no. 1; pp. 63 - 69
• Main Authors: Rojas, Fernanda Alvarez, Hirata, Aparecida Emiko, Saad, Mario J.A
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 25.10.2001
• Subjects: Animals; Diabetes Mellitus, Experimental - metabolism; Disease Models, Animal; Fasting - physiology; Insulin; Insulin - metabolism; Insulin - pharmacology; Insulin Receptor Substrate Proteins; Insulin Resistance - physiology; Intracellular Signaling Peptides and Proteins; IRS-2; Liver; Liver - drug effects; Liver - metabolism; Male; Muscle; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phosphoproteins - metabolism; Phosphorylation; Phosphotyrosine - metabolism; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Receptor, Insulin - metabolism; Signal Transduction - physiology; Muscle; IRS-2; Insulin; Liver
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(01)00597-4

Intracellular insulin signaling involves a series of alternative and complementary pathways created by the multiple substrates of the insulin receptor (IRS) and the various isoforms of the SH2 domain signaling molecules that can interact with substrate. In this study we investigated IRS-1 and IRS-2 tyrosine phosphorylation, their association with PI3-kinase and the phosphorylation of Akt, a serine–threonine kinase situated downstream to PI 3-kinase, in liver and muscle of two animal models of insulin resistance: 72 h of fasting and STZ-diabetic rats. There was an upregulation in insulin-induced IRS-1 and IRS-2 tyrosine phosphorylation and association with PI3-kinase in liver and muscle of both animal models of insulin resistance. However, Akt phosphorylation showed different regulation, increasing in fasting and decreasing in STZ-diabetic rats. Since an important difference between these two animal models of insulin resistance is the plasma glucose levels, we can suggest that in STZ diabetic rats, the reduction in Akt phosphorylation is probably related to hyperglycemia and may certainly contribute to the molecular mechanism of insulin resistance observed in these animals.