New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives

Abstract

Diabetes mellitus is a growing public health problem. In order to combat this disease, it is necessary to have deep knowledge of its pathophysiological mechanisms. The present project attempts to investigate features related to the development/progression of DM, seeking to expand preventive and therapeutic approaches for the control of glycemia and the development of chronic complications. In experimental models, the following will be investigated: 1) the effects of inflammatory mediators, endoplasmic reticulum stress pathway, sympathetic blockers, corticosteroids, estrogen, glycated albumin and AGEs upon glucose uptake and glucose transporter expression in muscle and adipose tissue, glucose efflux and proteins related to glucose metabolism in liver, and insulin secretion by pancreatic islets; 2) the relationship between nephropathy development and GLUTs, SGLTs, RAGE and AGE-R1 expression in kidney; 3) the effect of glycotoxicity, cAMP, AGEs and inflammatory mediators on renal HEK-293 cells; and 4) the role of GLUT4, lipid content, inflammatory activity, AGEs, oxidative stress and endoplasmic reticulum stress in the cardiomyopathy. As new therapeutic players, the effects of diacerein, estrogen receptor alpha agonist, cannabinoid receptor CB1 inhibitor, benfotiamine and sirtuin will be investigated. Furthermore, we will also investigate: 5) in human type 2 DM, the effect of acute exercise on glycemic control (by CGMS) and markers of oxidative stress and inflammatory activity, and the impact of resistance exercise on glycemic control and cardiovascular function; and 6) in human type 1 DM, the correlation between polymorphisms (SNPs) in genes related to glucose transport, AGEs production and oxidative stress and nephropathy; the correlation between polymorphonuclear cells RAGE/AGE-R1 and nephropathy; and the expression of GLUTs/RAGE/AGE-R1 in urinary sediment, as a marker of intra-renal activity of pathways related to the development/progression of nephropathy. We hope to characterize new preventive and therapeutic approaches, which will contribute to the health of diabetic subjects. (AU)