Coronary function in type 1 diabetic female rats: the effects of treatment with inhibitors of advanced glycation end-products (ages) and protein kinase c beta (PKC-beta)

Abstract

The pharmacologic approaches currently in clinical use have remained unsatisfactory in preventing the diabetic vascular complications and more innovative therapies are needed. The advanced glycation end products (AGEs) formation and the activation of protein kinase C are considerate important pathways involved in vascular complications associated with diabetes. Therefore, the aim of this study will be to investigate the coronary vascular responsiveness in type 1 diabetic female rats and the effects of co-treatment with insulin + pyridoxamine (AGEs inhibitor) and insulin + ruboxistaurin (PKC-beta inhibitor). Additionally, circulating factors such as glucose, insulin, estradiol, total cholesterol, triglycerides, creatinine, Hb-A1c, Nµ-carboxymethyl lysine (CML), cyclic GMP (GMPc), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), IL-1², IL-6, IL-10, TNF-±, TGF-²1, MCP-1, VEGF, leptin and adiponectin, as well as the protein expressions of eNOS, AGE, RAGE, AGER1, PKC-±, PKC-²1, PKC-²2, ER-± and ER-² (coronary artery) and adiponectin, leptin, IL-1², TNF-± e PGC1-± (epicardial adipose tissue) will be analyzed. Tissue nitric oxide (NO) production and reactive oxygen species (ROS) generation will be evaluated. (AU)