AbstractsMedical & Health Science

Introduction: There is significant mortality in the diabetic population due to cardiovascular complications. One of the characteristic biochemical changes often found in diabetes is the formation of advanced glycation end products (AGEs). AGEs are one of the primary ligands for the receptor of AGE (RAGE) and have previously been implicated in the initiation and maintenance of a pathological pro-inflammatory response primarily through NF-κB. The AGE-RAGE interaction has been directly linked to deleterious effects eventually leading to pathologies such as atherosclerosis and cardiomyopathy. Oxytocin, a peptide hormone, which induces parturition, has been shown to have cardioprotective properties. Activation of the oxytocin receptor can induce the shedding of RAGE thereby decreasing the inflammatory response.Objective: To identify differences in the metabolic and cardiac function by oxytocin treatment in animal models of type I and II diabetes mellitus and to explore the protective mechanism achieved following oxytocin therapy in both models.Methods: Experiments were performed in type I and II diabetic animal models and in H9c2 embryonic rat cardiac myoblasts. Four-week old Wistar rats were treated with a single dose of streptozotocin (65 mg/kg) to induce type I diabetes after two days, followed by oxytocin infusion (125 ng/kg/h) using osmotic Alzet pumps for six weeks. Similarly, four-week old db/db mice of type II diabetic phenotype were treated with oxytocin (125 ng/kg/h) for 12 weeks. After sacrifice, the heart and aorta were collected from control (non-diabetic), diabetic and oxytocin treated animals then stained for accumulation of collagen and polysaccharides. Protein levels were measured by Western blot. H9c2 cells were pre-treated with glyceraldehyde-AGE (100-400 μg/mL) for two hours followed by oxytocin (62.5 nM and 300 nM) for five hours. Cell viability was measured by a resazurin assay and protein expression through in-cell ELISA.Results: Oxytocin administration diminishes body weight changes and glycemia in type I and II diabetic animals. Heart weight was unaffected by oxytocin treatment in type I diabetic rats nor in type II diabetic mice. RAGE expression was also found to be significantly reduced upon oxytocin treatment in both type I diabetic (3.56 ± 1.01 fold vs. 1.10 ± 0.40 fold in treated animals, p<0.05) and type II diabetic (1.55 ± 0.05 fold vs. 1.13 ± 0.01 fold in treated animals, p<0.001). The expression of NF-κB was not elevated in type I diabetic rats but increased in type II diabetic mice. Elevation of NF-κB was associated to the increases in reactive oxygen species accumulation and reduction of cell apoptosis seen in the untreated db/db mice. These effects were reversed by oxytocin treatment. The treatment of H9c2 cells with AGEs did not present any effect on cell viability in a dose or time dependent manner. Cells pre-stimulated with AGEs showed significantly increased levels of phosphorylated NF-κB (p<0.05) but no changes in total NF-κB. Treatment with oxytocin also did not appear to…