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Lower expression of advanced glycation endproduts receptor-1 (AGER1) in peripheral blood mononuclear cells is associated with renal disease in type 1 diabetes patients

Grant number: 12/25490-8
Support type:Scholarships in Brazil - Master
Effective date (Start): May 01, 2013
Effective date (End): April 30, 2015
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal researcher:Maria Lucia Cardillo Corrêa Giannella
Grantee:Daniele Pereira dos Santos Bezerra
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives, AP.TEM


The role of hyperglycemia in the pathogenesis of macro- and microvascular complications in type 1 diabetes mellitus (T1DM) is already well established and the risk for complications is modulated by determinants such as genetic susceptibility, age at onset and duration of diabetes, hypertension, dyslipidemia, smoking and alcohol consumption. Several mechanisms were proposed to explain glucotoxicity as increased activation of polyol pathway, activation of protein kinase C and the hexosamine pathway and formation of advanced glycation end products (AGEs). AGEs irreversibly alter the structure of macromolecules, compromising its biological function. Moreover, the interaction with their specific receptor, RAGE, favors signal transduction pathways that culminate in the generation of reactive oxygen species. A second type of AGE receptor, the AGER-1, opposes the toxicity of AGEs, by stimulating cellular antioxidant activity and reducing inflammatory stress. There are few studies addressing the expression of AGE receptors and its correlation with chronic microvascular complications in T1DM. Our hypothesis is that a change in the balance between the expression of RAGE and AGER-1 in lymphomononuclear cells as well as the decrease of antioxidant defenses may reflect the degree of chronic microvascular complications. The objective of this project is to correlate in T1DM patients, the degree of microvascular complications (retinopathy, nephropathy and neuropathy) with: (1) expression of RAGE, AGER-1 and sirtuin 1 (a deacetylase that plays an important role in the pathogenesis of several degenerative diseases) in lymphomononuclear cells, (2) total antioxidant defenses and lipid peroxidation markers and (3) plasma concentrations of the carboximethyl-lysine (an AGE) and of total AGEs. Approximately 100 T1DM patients and 10 healthy controls matched for age and sex will be evaluated.

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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)
SANTOS-BEZERRA, DANIELE P.; MACHADO-LIMA, ADRIANA; MONTEIRO, MARIA BEATRIZ; ADMONI, SHARON N.; PEREZ, RICARDO V.; MACHADO, CLEIDE G.; SHIMIZU, MARIA HELOIZA; CAVALEIRO, ANA M.; THIEME, KARINA; QUEIROZ, MARCIA S.; MACHADO, UBIRATAN F.; GIANNELLA-NETO, DANIEL; PASSARELLI, MARISA; CORREA-GIANNELLA, MARIA LUCIA. Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients. Diabetes & Vascular Disease Research, v. 15, n. 1, p. 81-89, JAN 2018. Web of Science Citations: 3.
MONTEIRO, MARIA BEATRIZ; SANTOS-BEZERRA, DANIELE PEREIRA; THIEME, KARINA; ADMONI, SHARON NINA; PEREZ, RICARDO VESSONI; MACHADO, CLEIDE GUIMARAES; QUEIROZ, MARCIA SILVA; NERY, MARCIA; OLIVEIRA-SOUZA, MARIA; WORONIK, VIKTORIA; PASSARELLI, MARISA; GIANNELLA-NETO, DANIEL; MACHADO, UBIRATAN FABRES; CORREA-GIANNELLA, MARIA LUCIA. Thioredoxin interacting protein expression in the urinary sediment associates with renal function decline in type 1 diabetes. Free Radical Research, v. 50, n. 1, p. 101-110, JAN 2 2016. Web of Science Citations: 9.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BEZERRA, Daniele Pereira dos Santos. Lower expression of advanced glycation endproduts receptor-1 (AGER1) in peripheral blood mononuclear cells is associated with renal disease in type 1 diabetes patients. 2015. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina São Paulo.

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