Análise da expressão de células progenitoras pancreáticas em camundongos obesos tratados com IGF-1

Abstract

Diabetes mellitus is mainly characterized by a disruption in glucose homeostasis and is already recognized as a global epidemic. In pancreatic islets,  cells secrete insulin in response to glucose levels, to maintain normoglycemia. To sustain insulin demand,  cells present a dynamic balance between replication, hypertrophy, apoptosis and in certain conditions neogenesis from progenitor cells. When cell death is greater than the replacement is created a functional impairment and diabetes is established. It is of great interest to understand the mechanism of regeneration β cells, either by replication of preexisting βcells or neogenesis of progenitor pancreas cells. Therefore, we intend to evaluate the participation of progenitor cells in homeostasis of pancreatic islet of obese mice following treatment with IGF-1. In this study we use swiss mice which were separated in a control group, fed with standard diet, and obese group, fed with high-fat diet to induce obesity, since obesity promotes pancreatic islets hypertrophy with increasing insulin secretion. After 11 weeks of diet the mice were treated with IGF-1 for 7 consecutive days. Our results demonstrate that the obese group showed hypertrophic pancreatic islets as well as ultrastructural changes in β cells. There was a decrease in body weight and adiposity in obese mice treated with IGF-1. We also observed a higher rate of apoptosis of pancreatic cells in the obese group, which was minimized after IGF-1 treatment. Evaluation of Pdx1, an important transcription factor for formation and maintenance of β cells, showed a lower content in obese group. However, after treatment with IGF-1 the expression of Pdx1 was similar to the control group. Regarding the progenitor cells (CD105, c-Kit and CD133), we observed that only CD133 cells were present in pancreatic islets of obese animals and remained after treatment with IGF-1. Although we have not found significant expression of progenitor cells in mice treated with IGF-1, we believe their therapeutic potential through the reduction of obesity, and improvement of diabetes mellitus type 2.