Investigation about the role of NFºB and STAT1 pathways activated by cytokines on the decrease of insulin secretion in cachectic solid Ehrlich tumour-bearing mice

• Grant number: 13/08391-9
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2013
• End date: August 31, 2015
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: José Roberto Bosqueiro
• Grantee: José Roberto Bosqueiro
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil

Abstract

Cachexia, a syndrome that commonly affects patients with malignant neoplasm, is characterized by a severe imbalance in metabolic homeostasis, and, especially, on the mechanisms involved in glycemic homeostasis. In previous studies, we have shown that cachectic solid Ehrlich tumor-bearing mice (TSE) exhibited decreased insulin secretion as well as increased peripheral sensitivity to this hormone. We still found a significant increase in levels of cytokines such as IL-1 ², TNF-±, IFN-³, IL-6 and IL-8 in pancreatic islets, accompanied by lymphocyte infiltration. The establishment of systemic inflammation seems to be a crucial factor for the progression of cachexia in cancer, in particular by the presence of cytokines. However, there is no work in the literature that investigates the mechanisms that lead to changes in insulin secretion observed in patients with tumor or that correlates it to establishment of systemic inflammation. Based on the importance of insulin secretion for the control of metabolic homeostasis, identify mechanisms that are involved in this process becomes essential. So, is the proposal of this study to investigate the effects of high levels of cytokines pancreatic islets of TSE mice on the activity of important inflammatory pathways, particularly those related to apoptosis, in order to contribute to the understanding about their participation in reducing insulin secretory capacity of islets of these animals. To this end, the islets of Swiss control (CTL) and TSE mice with 14 days of tumor evolution will be examined to assess the participating of expression of proteins that belong to NFºB and STAT1 pathways, expression of genes involved in apoptosis, measurement of insulin secretion using specific blockers for components of the inflammatory pathways studied, as well as morphometric analyses as growth, proliferation and beta cell mass. (AU)