Scholarship 22/11249-9 - Fisiologia do sistema digestório, Microbioma gastrointestinal - BV FAPESP
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Slow intestinal transit and intestinal microbiota composition in the genesis of insulin resistance in Goto-Kakizaki rats

Grant number: 22/11249-9
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Start date until: December 01, 2022
End date until: August 31, 2026
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Rui Curi
Grantee:Gabriela Mandu Gimenes
Host 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
Associated scholarship(s):23/14878-0 - ASSOCIATION OF GUT MICROBIOTA WITH THE DIABETIC PHENOTYPE OF GOTO-KAKIZAKI RAT (A NON-OBESE DIABETIC MODEL), BE.EP.DD

Abstract

The Goto-Kakizaki (GK) rat spontaneously develops Type 2 Diabetes Mellitus (T2DM) but without obesity. In GK rats, we reported slow intestinal transit and increased small intestinal pro-inflammatory markers. The myenteric plexus is part of the enteric nervous system (ENS) and controls intestinal motility. The myenteric of small intestine pf GK rats has differences regarding the density of inhibitory neurons in the duodenum (decreased) and jejunum (increased). The diabetic state, in turn, causes marked changes in SNE and the intestinal microbiota. We believe that the slower intestinal transit (constipation) can trigger insulin resistance (IR) and T2DM in GK rats by promoting changes in the microbiota composition. We will investigate this hypothesis in the same animal at different ages (weaning- 21, 60, and 120 days). During the experimental period, we will measure the following parameters: intestinal motility by methylene blue gavage, determination of plasma LPS (lipopolysaccharides), metagenomic analysis of microbiota composition, and peripheral sensitivity to insulin through glucose and insulin tolerance tests. An antibiotic cocktail will be administered to the animals from weaning to 60 days old to induce depletion of the intestinal microbiota in GK and Wistar rats. With this protocol, it will be possible to investigate the influence of the intestinal microbiota on the genesis of the diabetic phenotype of GK rats. After the treatment, peripheral insulin sensitivity and intestinal permeability and motility will be evaluated. The total population of neurons (HuC/D) and the inhibitory (nNOS) and excitatory (ChAT) subpopulations as well as the glia (S100) of the myenteric plexus will be studied by immunofluorescence in a whole mount preparation. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GIMENES, GABRIELA MANDU; PEREIRA, JOICE NAIARA BERTAGLIA; DA SILVA, ELIANE BORGES; DOS SANTOS, ALEF ARAGAO CARNEIRO; RODRIGUES, THAIS MARTINS; SANTANA, GIOVANNA DE OLIVEIRA; SCERVINO, MARIA VITORIA MARTINS; PITHON-CURI, TANIA CRISTINA; HIRABARA, SANDRO MASSAO; GORJAO, RENATA; et al. Intestinal Motility Dysfunction in Goto-Kakizaki Rats: Role of the Myenteric Plexus. CELLS, v. 13, n. 19, p. 15-pg., . (19/01942-6, 18/09868-7, 22/11249-9)

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