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Neurochemical characterization of mioenteric plexus of Goto-Kakizaki rat intestine

Grant number: 19/01942-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): July 01, 2019
Effective date (End): June 30, 2021
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Rui Curi
Grantee:Gabriela Mandu Gimenes
Home Institution: Centro de Ciências Biológicas e da Saúde. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
Associated research grant:18/09868-7 - Cellular and molecular mechanisms of insulin resistance and inflammation in obese Wistar rats and lean Goto-Kakizaki rats: causes and associations with diet and physical exercise, AP.TEM

Abstract

The association between diabetes mellitus type 2 (DM2), insulin resistance (IR), and obesity is very well established. Under these conditions, a low-grade systemic inflammation is reported that reduces the activity of the insulin signaling pathway. The gastrointestinal tract (GIT) activity is controlled by an intrinsic nerve network, the enteric nervous system (ENS), which is composed of two plexuses: the myenteric and the submucous. Long-term diabetes mellitus causes complications in various organs and tissues including GIT and ENS. The Goto-Kakizaki (GK) rats develop DM2 spontaneously, however, without presenting obesity. This experimental model allows to be inquiring the mechanisms involved in the development of type 2 diabetes mellitus without the participation of adipose tissue that often masks the interpretation of the results and the discrimination of the causes associated with the disease. Preliminary findings (unpublished data) are indicative that GK rats have marked morphofunctional variations in neurons of the intestinal myoenteric plexus. This organ may therefore play a central role in triggering IR in it impairs intestinal secretion and nutrient absorption as well as the inflammatory state of this organ. The aim of this study is to investigate the involvement of the myoenteric plexus cells (neurons and glia) of the small and large intestines of Goto-Kakizaki rats during the establishment of IR and DM2. Control animals and GKs will be studied at weaning (without IR) and after 60 (initial IR) and 120 (well established) days age. The contribution/participation of the ENS for the establishment of IR and DM2 will be investigated through immunohistochemical techniques for morpho-quantitative analysis and characterization of the chemical "code" of myoenteric neurons and glial cells as well as analysis of intestinal motility.