Evaluation of the expression of components of NAD (P) H oxidase in muscle, liver and adipose tissue in an experimental model of insulin resistance after treatment with losartan.

• Grant number: 10/09254-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2010
• End date: July 31, 2011
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Aparecida Emiko Hirata
• Grantee: Mariana Corrêa de Melo Bertholdo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 09/51893-0 - The role of NAD(P)H oxidase in the molecular mechanisms of pancreatic beta cell physiology, AP.TEM

Abstract

Diabetes Mellitus is a heterogeneous group of metabolic diseases characterized by hyperglycemia. In the most common form of the disease, type 2, the etiologies are not yet established. There is a genetic component, yet ill-defined and obesity, physical inactivity and aging trigger or accelerate the onset of the disease. DM2 appears to be polygenic, with polymorphisms that should facilitate the installation of insulin resistance, and the mass reduction of B cells In patients with DM2, hyperglycemia and other metabolic disorders exacerbate insulin resistance and decrease insulin secretion, making the investigation of the pathogenic sequence in this form of diabetes. The main problem of this type of diabetes is resistance to insulin, which leads to hyperglycemia, plus there is a defect related to insulin secretion. Insulin resistance in the liver is expressed by excessive production of fasting glucose and reduced liver uptake of glucose in the absorptive period, which results in an "escape" of glucose responsible for the exaggerated postprandial hyperglycemia. Insulin resistance at the peripheral level is reflected by reduction in glucose uptake by muscle even after exposure to normal or high insulin. While this resistance to insulin promotes a decrease in the binding of insulin to its receptors in patients with T2DM, the most serious forms of the disease (fasting hyperglycemia> 180 mg%) coexisting defects at receptor and post receptor, and prominent defect occurs intracellularly (post-receptor). Insulin resistance is considered the main physiopathological characteristic of the metabolic syndrome Several mechanisms linking insulin resistance and hypertension, and these factors often associated with progress in the development of diabetes and cardiovascular disease. Metabolic syndrome is characterized by the association of risk factors for cardiovascular disease, peripheral vascular disease and diabetes. It is based on resistance to insulin, hypertension, abdominal obesity and dyslipidemia. Given the large body of evidence linking hypertension, insulin resistance and the development of T2DM, and a possible autocrine and / or paracrine activity of Ang II on different tissues is likely that the presence of the Renin Angiotensin System (RAS) has some important function in such conditions. Obesity and diabetes are considered states whose pro-inflammatory signaling pathways are involved in the development of the state of insulin resistance. Pro-inflammatory factors induce the production of ROS via activation of NAD (P) H oxidase and this is able to activate transcription of different pro-inflammatory genes. Therefore, the objective of this study is to evaluate the treatment effect of losartan on protein expression of components of NAD (P) H oxidase and AT 1 in liver, muscle and adipose tissue of experimental model of insulin resistance.