Tesis doctoral de María Jiménez González
Application of cardiotrophin in an experimental model of diabetes mellitus cardiotrophin (ct-1) is a cytokine member of the il-6 family, which was originally isolated from the heart, where it has been shown to play an important role in apoptotic protection of cardiomyocytes and heart hypertrophy. Its beneficial properties have been also described in other organs such as liver and neuromuscular tissue. In the present study, we investigated whether ct-1 can confer protection against pro-apoptotic stimuli in pancreatic beta cells and its role in insulin secretion and diabetes development. first, we analysed the apoptotic signal in min6b1 cell line and freshly isolated murine pancreatic islets in the presence of ct-1. Also, we have determined its role on in vitro insulin secretion and, by using pharmacological inhibitors, we have analyzed the intracellular pathways through which ct-1 may affect insulin secretion in min6b1 cells. Furthermore, we investigated the development of diabetes in ct-1-/- mice using a streptozotocin (stz)-induced diabetes model. we found that the ct-1 presents a protective role in the insulinoma cell line min6b1 and murine islets under the proapoptotic stimuli of serum deprivation, which correlates with an increment in the expression of the protein bcl-xl, as well as a synergestic effect on insulin secretion in combination with glucose. Furthemore, the ct-1-/- mice are more prone to develop diabetes than the wt mice when diabetes is induced by stz and their glucose tolerance test showed impaired plasma glucose clearence. the results obtained from both in vitro and in vivo experiments shown that the expression of ct-1 exerts a protective effect in the pancreas. Moreover, the absence of ct-1 expression plays an important role in the development of diabetes.
Datos académicos de la tesis doctoral «Aplicación de la cardiotrofina en un modelo experimental de diabetes mellitus«
- Título de la tesis: Aplicación de la cardiotrofina en un modelo experimental de diabetes mellitus
- Autor: María Jiménez González
- Universidad: Navarra
- Fecha de lectura de la tesis: 13/05/2011
Dirección y tribunal
- Director de la tesis
- Felipe Luis Prosper Cardoso
- Tribunal
- Presidente del tribunal: Francisco Martín bermudo
- deborah Burks (vocal)
- miriam Ramirez dominguez (vocal)
- José Manuel Fernández-real lemos (vocal)