STUDY ABOUT THE MECHANISMS INVOLVED IN THE DEVELOPMENT OF INSULIN RESISTANCE IN RATS WITH PERIAPICAL LESION

• Grant number: 14/17619-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2015
• End date: October 31, 2018
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Doris Hissako Matsushita
• Grantee: Renato Felipe Pereira
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated scholarship(s): 16/07151-2 - Role of Muscle Ceramides on Mitochondrial Function and Insulin Action, BE.EP.DR

Abstract

Currently, there is some consensus within the dentistry area related to the fact that chronic inflammation in teeth may eventually lead to systemic disorders. Periapical lesion (PL) is characterized as an oral inflammation and it is associated with increased levels of proinflammatory cytokines such as IL-6 and TNF-±, that possibly induce insulin resistance. Insulin resistance can be defined as the state in which there is a decreased tissue glucose uptake in response to insulin stimulus, however, the mechanisms that cause insulin resistance are not fully understood. Previous studies from our laboratory observed that PL promotes increased plasma concentrations of TNF- ±, impairments in insulin signal transduction and reduced GLUT4 content in plasma membrane in skeletal muscle tissue, showing a relationship between PL and insulin resistance. These findings highlight the need for further studies to verify the mechanisms involved in these alterations. This study, performed in rats with PL, aimed: 1) to evaluate the total content (JNK, IKK±/b, TNF-a)and phosphorylation status (JNK, IKK±/b) of inflammatory proteins in skeletal muscle tissue; 2) to verify the presence of infiltrated macrophages(proteína F4/80) in this tissue; 3) to quantify the expression of transcription factors involved in the differentiation of lymphocytes in spleen tissue (T-bet, GATA-3 e FOXP3); 4) to analyze the plasma concentrations of LPS, HSP70, INFg, TNF-a, IL-4, TGF-b. For this purpose, 45 Wistar rats (2 months old) will be distributed into three groups: a) control rats without PL; b) rats with induced PL in the first upper right molar (only one lesion); c) rats with induced PL in first and second molars of the upper and lower right side (total of four lesions) employing a drill carbon steel with a sphere of 0.1 mm in the edge. Statistical analysis will be performed by analysis of variance (ANOVA) followed by Tukey test. The significance level adopted will be 5% (alpha = 5%).

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)

CHAURASIA, BHAGIRATH; TIPPETTS, TREVOR S.; MONIBAS, RAFAEL MAYORAL; LIU, JINQI; LI, YING; WANG, LIPING; WILKERSON, JOSEPH L.; SWEENEY, C. RUFUS; PEREIRA, RENATO FELIPE; SUMIDA, DORIS HISSAKO; et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science, v. 365, n. 6451, p. 386+, JUL 26 2019. (14/17619-6)

PEREIRA, RENATO FELIPE; ANGELO CINTRA, LUCIANO TAVARES; LATTARI TESSARIN, GESTTER WILLIAN; CHIBA, FERNANDO YAMAMOTO; DE LIMA COUTINHO MATTERA, MARIA SARA; SCARAMELE, NATALIA FRANCISCO; SAORI TSOSURA, THAIS VERONICA; ERVOLINO, EDILSON; PENHA DE OLIVEIRA, SANDRA HELENA; SUMIDA, DORIS HISSAKO. Periapical Lesions Increase Macrophage Infiltration and Inflammatory Signaling in Muscle Tissue of Rats. JOURNAL OF ENDODONTICS, v. 43, n. 6, p. 982-988, JUN 2017. (14/17619-6)

PEREIRA, RENATO FELIPE; LATTARI TESSARIN, GESTTER WILLIAN; CHIBA, FERNANDO YAMAMOTO; DE LIMA COUTINHO MATTERA, MARIA SARA; PEREIRA, AMANDA GOMES; SAORI TSOSURA, THAIS VERONICA; BALERA BRITO, VICTOR GUSTAVO; FUJII DE OLIVEIRA, RENAN AKIRA; ERVOLINO, EDILSON; PENHA DE OLIVEIRA, SANDRA HELENA; et al. pical periodontitis promotes insulin resistance and alters adaptive immunity markers in rat. SAUDI DENTAL JOURNAL, v. 33, n. 8, p. 979-986, DEC 2021. (16/24829-2, 14/17619-6, 18/17795-0, 14/26517-2)