Evaluation of glucose transporters GLUT1 and GLUT4 in spontaneously diabetic mice cardiomyocytes primary culture

• Grant number: 13/03542-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2013
• End date: September 30, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Dulce Elena Casarini
• Grantee: Mônica Rika Nakamura
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 10/51904-9 - Renin angiotensin and kallikrein kinin systems in hypertension, obesity, diabetes, desnutrition and sepsis: molecular, cellular and physiopathologic mechanisms, AP.TEM

Abstract

Diabetes Mellitus is a group of metabolic disorders characterized by hyperglycemia which may be classified as type 1 and 2. Diabetes mellitus type 1 (DM1) is an autoimmune disease characterized by a deficiency in the secretion of insulin due to the destruction of pancreatic beta cells. In type 2 diabetes mellitus (DM2), insulin is secreted normally but there is a resistance to insulin, or the body can't use insulin properly. Recently, the World Health Organization acknowledged that the disease is epidemic. In spite of the incidence of DM1 being lower than the DM2, high rates of morbidity, mortality, and disability make their work relevant to study. DM1, although it can occur at any age, DM1 usually occurs during puberty and most patients are under 20 years of age. The use of exogenous insulin and a special diet to which glucose levels are controlled becomes essential. The heart is potentially impaired in people with type 1 diabetes. It is known that disturbances of glucose metabolism can cause complications involving heart disease called diabetic cardiomyopathy, including hypertension, coronary artery disease, and heart failure, and 75% of diabetic patients die of some event cardiovascular. Among the many heart problems that arise as a result of DM, diabetic cardiomyopathy has been recognized as a specific cardiac disease, which occurs in approximately 30% of type 1 diabetic patients. At the cellular level, it was shown that diabetes impairs the function of contractile cardiomyocytes, especially for causing structural and functional changes in the regulation of calcium (Ca2 +) intracellular. It is believed that there are primary changes of the myocardium in patients with diabetes mellitus, such as collagen accumulation in the perivascular region and thickening of the basement membrane-related metabolic disorder, independent of ischemia secondary to disease coronary. The glucose transport into the cells is the responsibility of glucose transporters (GLUT) having highlight transporters GLUT1 and GLUT 4. The GLUT1 transporter is widely distributed throughout the body and it is responsible for the basal level of glucose in the cell. GLUT1 has a high transport capacity and high affinity for the glucose molecule while maintaining the glucose level within the cell. Besides not presenting activity regulated by insulin. The glucose transporter protein 4 (GLUT4) is sensitive to insulin, and in the absence of insulin stimulation, only 10% is present in the plasma membrane, and 90% is present in microsomal membranes which are small vesicles intracellular. It was observed that in patients with DM1, the GLUT4, which is sensitive to insulin, the deficiency of insulin stimulation makes complicates the entry of glucose into cells. The GLUT4 is present in the striated muscles heart. One of the most suitable animal models for the study of DM1 is a strain of mice spontaneously diabetic NOD mice (non-obese diabetic). From the spontaneously diabetic mice, we intend to evaluate the expression of glucose transporters GLUT1 and GLUT2 in the primary culture of cardiomyocytes. (AU)