Investigating the role of insulin in different infections in diabetic and healthy animals

Abstract

It is known that type I diabetic patients have a higher predisposition to secondary infections. Previous studies from our group found that part of this predisposition is a function of the relative lack of insulin. Diabetic nephropathy is a major complication of diabetes mellitus and may progress to chronic kidney disease characterized by kidney failure. Therefore dialysis has been increasingly used. Peritoneal dialysis (PD) is the alternative to replace hemodialysis, but despite technological innovations, peritonitis is still a major cause of hospitalization and discontinuation of PD. The main cause of this type of peritonitis are Gram-positive bacteria, Staphylococcus aureus was associated with more severe manifestations, the greater the need for handling of the catheter, with a high risk of hospitalization and death. So the first part of this project is to study the role of insulin in the modulation of peritonitis caused by S. aureus. The second part of this project is to study the effect of insulin in a model of systemic mycosis caused by Paracoccidioides brasiliensis. The paracoccidioidomycosis (PCM) is a systemic disease caused by P. brasiliensis fungus that exhibits thermal dimorphism. The P. brasiliensis interacts with antigen presenting cells (APC), changing their major biological functions. Among the APC cells are macrophages that play an important role in the induction and regulation of immune response. Recently it was observed that the phagocytic capacity of these cells in diabetic animals IgG opsonized targets is decreased compared to healthy animals.Taken them together, these projects will analyze the molecular mechanisms (production/release of cytokines), intracellular (signaling pathways), the expression of TLR receptors involved and the phagocytic activity of macrophages and microbicide. (AU)