Variables on glycemic control and pathogenesis of diabetic nephropathy: research on the phenomenon of metabolic memory

• Grant number: 12/08617-4
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2013
• End date: December 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Ana Paula de Melo Loureiro
• Grantee: Antonio Anáx Falcão de Oliveira
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes mellitus is considered a serious global health problem, and its complications have a major impact on population mortality. Diabetic nephropathy is a major complication of metabolic disease, characterized primarily by a progressive decline in the rate of glomerular filtration, persistent proteinuria, and hypertension. Several mechanisms have been proposed as important in the pathogenesis and progression of diabetic nephropathy. Hyperglycemia is closely associated with oxidative stress, with increase in pro-inflammatory cytokines such as IL-1, IL-6 and TNF-a, growth factors, such as TGF-b, and formation of advanced glycation end products. Considering the fact that even after glycemic control there is the occurrence of diabetes complications, recent studies have proposed the phenomenon known as metabolic memory to explain this fact. From this perspective, this study will evaluate the modulation of a series of markers related or possibly related to diabetic nephropathy in conditions of hyperglycemia and early and late glycemic control by the oral antidiabetic metformin in combination with insulin. Markers related to oxidative stress (DNA lesions 8-oxodGuo, 1,N2-edGuo, 1,N6-edAdo, protein expression of SIRT-1, AMPK, Bax, TGF-b, MKK 3/6, MKP-1 and p38), inflammation (DNA lesions 8-NO2-dG, 8-Cl-dG and IL-6, TNF-a, NF-kB) and the advanced glycation process (glycated hemoglobin and N-(carboxymethyl)lysine) will be evaluated in a model of diabetic rats, as well as the expression of target genes (PPARGC1A, TGF-², TSP-1, MKP-1 and UNC13B) and their possible epigenetic regulation (methylation or demethylation of CpG islands) with or without control of hyperglycemia. The aim here is thus to elucidate new pathways involved in the process of metabolic memory that have an important role in the development of diabetic nephropathy, in order to contribute to its control. (AU)

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)

DE OLIVEIRA, TIAGO FRANCO; FELCAO DE OLIVEIRA, ANTONIO ANAX; LEMOS, MIRIAM; VERAS, MARIANA; NASCIMENTO SALDIVA, PAULO HILARIO; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE MELO LOUREIRO, ANA PAULA. Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, n. 147, MAY 2019. (13/07937-8, 11/09891-0, 12/08617-4, 12/21636-8, 12/08616-8, 12/22190-3)

FALCAO DE OLIVEIRA, ANTONIO ANAX; DE OLIVEIRA, TIAGO FRANCO; DIAS, MICHELLE FRANCINI; GENNARI MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; VERAS, MARIANA; LEMOS, MIRIAM; MARCOURAKIS, TANIA; NASCIMENTO SALDIVA, PAULO HILARIO; MELO LOUREIRO, ANA PAULA. Genotoxic and epigenotoxic effects in mice exposed to concentrated ambient fine particulate matter (PM2.5) from SAo Paulo city, Brazil. PARTICLE AND FIBRE TOXICOLOGY, v. 15, OCT 19 2018. (12/08617-4, 12/08616-8, 11/09891-0, 12/22190-3, 12/21636-8, 13/07937-8)

DE CARVALHO, ALINE MARTINS; FALCAO DE OLIVEIRA, ANTONIO ANAX; DE MELO LOUREIRO, ANA PAULA; FIGARO GATTAS, GILKA JORGE; FISBERG, REGINA MARA; MARCHIONI, DIRCE MARIA. Arginine intake is associated with oxidative stress in a general population. NUTRITION, v. 33, p. 211-215, JAN 2017. (12/08617-4, 14/04607-0, 12/10965-0, 09/15831-0)

DE OLIVEIRA, TIAGO FRANCO; FELCAO DE OLIVEIRA, ANTONIO ANAX; LEMOS, MIRIAM; VERAS, MARIANA; NASCIMENTO SALDIVA, PAULO HILARIO; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE MELO LOUREIRO, ANA PAULA. Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter. JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, v. N/A, n. 147, p. 19-pg., 2019-05-01. (13/07937-8, 12/22190-3, 12/08616-8, 11/09891-0, 12/08617-4, 12/21636-8)

DE OLIVEIRA, ANTONIO ANAX F.; DE OLIVEIRA, TIAGO F.; BOBADILLA, LARISSA L.; GARCIA, CAMILA C. M.; BERRA, CAROLINA MARIA; DE SOUZA-PINTO, NADJA C.; MEDEIROS, MARISA H. G.; DI MASCIO, PAOLO; ZATZ, ROBERTO; LOUREIRO, ANA PAULA DE M.. Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory. SCIENTIFIC REPORTS, v. 7, JAN 12 2017. (12/08617-4, 13/11747-0, 12/21636-8)

DE OLIVEIRA, TIAGO FRANCO; MEDEIROS DA SILVA, AMANDA LUCILA; DE MOURA, RAFAELA ALVES; BAGATTINI, RAQUEL; FALCAO DE OLIVEIRA, ANTONIO ANAX; GENNARI DE MEDEIROS, MARISA HELENA; DI MASCIO, PAOLO; DE ARRUDA CAMPOS, IVAN PERSIO; BARRETTO, FABIANO PRADO; HENRIQUES BECHARA, ETELVINO JOSE; et al. Luminescent threat: toxicity of light stick attractors used in pelagic fishery. SCIENTIFIC REPORTS, v. 4, JUN 19 2014. (06/56530-4, 12/21636-8, 12/08616-8, 12/08617-4, 09/54816-6, 13/07937-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

OLIVEIRA, Antonio Anáx Falcão de. The hyperglycemic memory in diabetic kidney: metabolic, molecular, and epigenetic marks. 2017. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.