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In vitro modulation of intestinal epithelial barrier mediated by tight junctions: effect of exposure to nutrients (glucose and fatty acids), insulin and bacterial microbiota of prediabetic animals

Grant number: 13/15676-0
Support Opportunities:Regular Research Grants
Duration: December 01, 2013 - March 31, 2016
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Carla Beatriz Collares Buzato
Grantee:Carla Beatriz Collares Buzato
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Tight Junction (TJ) mediates epithelial cell-cell interaction, performing an essential role in diffusion barrier through the paracellular pathway in intestinal epithelia, avoiding the entry of toxins and harmful bacteria into the organism. It has been suggested that alterations to the intestinal epithelial barrier may be involved in the obesity-associated type 2 diabetes mellitus (T2DM) pathogenesis, although the underlying mechanisms are not yet known. The objectives of the present project are: 1) to investigate the direct effect of components found at high concentrations within high fat-containing diet (glucose and fatty acids) or those that can be increased/altered systemically in the prediabetic state (glucose, fatty acids, insulin and microbiota) on the epithelial barrier function of intestinal and non-intestinal cell lines; and 2) to study the intracellular mechanisms involved in the putative tight junction impairment at these experimental conditions. To accomplish these goals epithelial cell lines, Caco-2 (human epithelial colorectal adenocarcinoma cells), IEC-6, IEC-18 (from small intestine of rat) and MDCK (derived of canine kidney cells) will be used. We will employ electrophysiological, biochemical (measurement of transepithelial electrical resistance and transepithelial flow of extracellular markers), immunocytochemical (to analyse the cellular distribution of some TJ-associated proteins, such as claudins, occludin, tricellulin and ZO-1) and molecular biology methods (Western Blotting and qPCR to determinate degree of genic and protein expression of TJ proteins). We believe that the development of this project will contribute to support research projects in our laboratory employing in vivo T2DM model, besides giving insights on the regulatory mechanisms of intestinal epithelial barrier and its putative relation with type 2 diabetes development. (AU)

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Scientific publications (6)
(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)
OLIVEIRA, R. B.; CANUTO, L. P.; COLLARES-BUZATO, C. B.. Intestinal luminal content from high-fat-fed prediabetic mice changes epithelial barrier function in vitro. Life Sciences, v. 216, p. 10-21, . (18/02118-2, 13/15676-0)
MONGELLI-SABINO, B. M.; CANUTO, L. P.; COLLARES-BUZATO, C. B.. Acute and chronic exposure to high levels of glucose modulates tight junction-associated epithelial barrier function in a renal tubular cell line. Life Sciences, v. 188, p. 149-157, . (13/15676-0)
DE OLIVEIRA, RICARDO BELTRAME; MATHEUS, VALQUIRIA APARECIDA; CANUTO, LEANDRO PEREIRA; DE SANT'ANA, ARIANE; COLLARES-BUZATO, CARLA BEATRIZ. Time-dependent alteration to the tight junction structure of distal intestinal epithelia in type 2 prediabetic mice. Life Sciences, v. 238, . (18/02118-2, 13/15676-0)
CANUTO, LEANDRO P.; COLLARES-BUZATO, CARLA B.. Increased osmolality enhances the tight junction-mediated barrier function in a cultured renal epithelial cell line. Cell Biology International, v. 43, n. 1, p. 73-82, . (13/15676-0)
COLLARES-BUZATO, CARLA B.; CARVALHO, CAROLINA P. F.. Is type 2 diabetes mellitus another intercellular junction-related disorder?. Experimental Biology and Medicine, v. 247, n. 9, p. 13-pg., . (18/02118-2, 14/22206-2, 13/15676-0, 10/50789-1, 15/25442-1)
MATHEUS, V. A.; MONTEIRO, L. C. S.; OLIVEIRA, R. B.; MASCHIO, D. A.; COLLARES-BUZATO, C. B.. Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice. Experimental Biology and Medicine, v. 242, n. 12, p. 1214-1226, . (13/15676-0)

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