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The role of Insulin Degrading Enzyme (IDE) in insulin resistance induced by cafeteria diet in Swiss mice

Grant number: 12/01271-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2012
Effective date (End): September 30, 2013
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Luiz Fernando de Rezende
Grantee:Patricia Brandimarti
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:11/09012-6 - Molecular mechanisms involved in the dysfunction and death of pancreatic beta cells in Diabetes Mellitus: strategies for the prevention of islet dysfunction and for islet mass recuperation in different cellular and animal models, AP.TEM

Abstract

INTRODUCTION: Obesity is a public health problem. Obese individuals are more prone to developing chronic diseases such as Hypertension, Arteriosclerosis and Diabetes Mellitus type 2 (DM2). Cafeteria diet is a robust model for the study of obesity as high consumption of fat is followed by an increase in plasma concentration of non-esterified fatty acids (NEFA). NEFAs are known to modulate insulin degradation and therefore may be involved in changes in insulin clearance associated with DM2.OBJECTIVE: Since IDE (Insulin Degrading Enzyme) is the main responsible for insulin degradation process, our goal is to investigate changes to this degradation, its time-course and its association with IDE and insulin resistance caused by the cafeteria diet in Swiss mice.MATERIALS AND METHODS: Animals will be divided into control (CON) and cafeteria (CAF) groups. After 70 days of their birth, the mice will receive standard feed and water ad libitum (CON) or modified feed and soft drink ad libitum (CAF) for 60 days, during which will be weekly evaluated weight, consumption and fasting glucose. After this period, biochemical plasma parameters, GTT, ITT and insulin clearance will be evaluated, and then the animals will be sacrificed and their organs collected for weighing, evaluation of gene (Real-Time RT-PCR) and protein (Western-blot) expression. The results will be analyzed for statistical significance (mean ± SE).EXPECTED RESULTS: It is expected to observe changes in insulin clearance and liver IDE expression and activity of animals fed with cafeteria diet associated with changes in peripheral sensitivity to insulin.