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The role of cytokine activated NFkB and STAT1 pathways in impairment of insulin secretion by cachectic solid Ehrlich carcinoma‐bearing mice. (LB762)
Author(s) -
Violato Natalia,
Bosqueiro José Roberto
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb762
Subject(s) - inflammation , islet , cachexia , endocrinology , apoptosis , cytokine , medicine , pancreatic islets , insulin , glucose homeostasis , biology , cancer research , pancreatic cancer , socs3 , cancer , insulin resistance , stat3 , biochemistry
The establishment of systemic inflammation seems to play a pivotal role in cancer cachexia progression, mainly by cytokine presence. However, there are no studies assessing the mechanisms responsible for the alterations in insulin secretion in cancer cachexia or correlating these alterations with inflammation in islet. Considering the importance of insulin secretion to metabolic homeostasis control, to identify mechanisms involved in this process in cachexia became important. Thus, in this study we propose to investigate the effects of the high cytokine levels present in cachectic syndrome in pancreatic islets function using solid Ehrlich carcinoma‐bearing mice and the participation of important inflammatory pathways, notably apoptotic pathways, searching for evidence that could indicate the involvement of islet inflammation in the diminished insulin secretion capacity exhibited by these animals. For that, pancreatic islets isolated from Swiss mice (CTL) and tumor‐bearing mice (SET) with 14 days of tumor inoculation were analyzed to evaluate the expression of proteins belonging to NFκB and STAT1 pathways. We analyzed proteins of IKK complex, JAK 1 and 2, STAT1, PUMA, FAS, c‐Myc, BAX, caspase 3 and 9, PDX‐1, and Bcl‐2. The results showed an increase in the expression of the pro‐apoptotic proteins BAX, c‐Myc, FAS, PUMA, caspase 3 and caspase 9. By the other hand, cachetic animals showed decreased expression of the anti‐apoptotic proteins Bcl‐2 and PDX‐1 indicating a possible increase of pancreatic islets apoptosis. These finds are very important in this scenario and will help us to clarify the mechanisms involved in diminished insulin secretion in cancer cachetic animals. Grant Funding Source : FAPESP