Avaliação de parâmetros renais, hemostáticos e inflamatórios e do efeito do tratamento com Peptídeo C em modelo animal de Diabetes mellitus tipo 1

• Ano de defesa: 2017
• Autor(a) principal: Michelle Teodoro Alves
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE BIOLOGIA GERAL; Programa de Pós-Graduação em Genética; UFMG
• Palavras-chave em Português: Fator de von Willebrand; ADAMTS13; Peptídeo C; Diabetes tipo 1; Inflamação; Genética; Diabetes mellitus tipo 1; Proteína ADAMTS13
• Link de acesso: http://hdl.handle.net/1843/38207; https://orcid.org/0000-0003-0604-9430

In diabetic patients, high plasma levels of von Willebrand factor (vWF), and reduced ADAMTS13 and C peptide have been associated to diabetes mellitus complications. The present study aims to investigate renal, hemostatic and inflammatory alterations in animal model of type 1 diabetes (T1DM) induced by streptozotocin and to evaluate the role of C peptide on these alterations in diabetic renal disease. Kidney alteration in diabetic mice was characterized by glomerular hyperfiltration, with increased urinary albumin excretion rate and creatinine, which is commonly observed in the initial phase of diabetic nephropathy. There was no significant difference between the levels of ADAMTS13 and vWF in plasma, however, ADAMTS13 urinary levels were significantly higher in the diabetic group compared to the control. Moreover, there was an increase in hepatic ADAMTS13 gene expression in diabetic group. Furthermore, urinary levels of ADAMTS13 correlated with glucose levels, creatinine and urinary albumin excretion, as well as inflammatory cytokines showing that the loss of protease is proportional to glycemia, renal dysfunction and inflammation. Treatment with C peptide is not able to reduce glycemia and renal excretion of albumin, creatinine and ADAMTS13. On the other hand, C peptide seems to reduce the renal inflammatory process, since it is observed a significantly reduction in IL17 and IL10 loss in the treated diabetic group when compared to the diabetic group not treated with C peptide. Moreover, there were increase in renal IL10 and ADAMTS13 gene expression. We conclude that in the animal model of T1DM there is no change in plasma levels of vWF and ADAMTS13, despite the increased urinary loss of ADAMTS13, suggesting that increased liver gene expression is an important factor in maintaining plasma levels of this protease. In addition, the loss of ADAMTS13 in the urine follows the evolution of renal disease, as well as metabolic and inflammatory complications of diabetes. Furthermore C-peptide may have an anti-inflammatory effect in diabetic kidney.