Investigating the role of insulin in different infections in diabetic and healthy animals

• Grant number: 14/05214-1
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2015
• End date: February 28, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Joilson de Oliveira Martins
• Grantee: Joilson de Oliveira Martins
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

It is known that type I diabetic patients have a higher predisposition to secondary infections. Previous studies from our group found that part of this predisposition is a function of the relative lack of insulin. Diabetic nephropathy is a major complication of diabetes mellitus and may progress to chronic kidney disease characterized by kidney failure. Therefore dialysis has been increasingly used. Peritoneal dialysis (PD) is the alternative to replace hemodialysis, but despite technological innovations, peritonitis is still a major cause of hospitalization and discontinuation of PD. The main cause of this type of peritonitis are Gram-positive bacteria, Staphylococcus aureus was associated with more severe manifestations, the greater the need for handling of the catheter, with a high risk of hospitalization and death. So the first part of this project is to study the role of insulin in the modulation of peritonitis caused by S. aureus. The second part of this project is to study the effect of insulin in a model of systemic mycosis caused by Paracoccidioides brasiliensis. The paracoccidioidomycosis (PCM) is a systemic disease caused by P. brasiliensis fungus that exhibits thermal dimorphism. The P. brasiliensis interacts with antigen presenting cells (APC), changing their major biological functions. Among the APC cells are macrophages that play an important role in the induction and regulation of immune response. Recently it was observed that the phagocytic capacity of these cells in diabetic animals IgG opsonized targets is decreased compared to healthy animals.Taken them together, these projects will analyze the molecular mechanisms (production/release of cytokines), intracellular (signaling pathways), the expression of TLR receptors involved and the phagocytic activity of macrophages and microbicide. (AU)

Scientific publications

(15)

(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)

BELLA, LEONARDO M.; FIERI, ISIS; TESSARO, FERNANDO H. G.; NOLASCO, EDUARDO L.; NUNES, FERNANDA P. B.; FERREIRA, SABRINA S.; AZEVEDO, CAROLINA B.; MARTINS, JOILSON O.. Vitamin D Modulates Hematological Parameters and Cell Migration into Peritoneal and Pulmonary Cavities in Alloxan-Diabetic Mice. BIOMED RESEARCH INTERNATIONAL, 2017. (13/20904-1, 12/23998-4, 14/05214-1, 10/02272-0)

RAJASEKARAN, SUBU SURENDRAN; KIM, JAEYOON; GABOARDI, GIAN-CARLO; GROMADA, JESPER; SHEARS, STEPHEN B.; DOS SANTOS, KAREN TIAGO; NOLASCO, EDUARDO LIMA; FERREIRA, SABRINA DE SOUZA; ILLIES, CHRISTOPHER; KOHLER, MARTIN; et al. Inositol hexakisphosphate kinase 1 is a metabolic sensor in pancreatic beta-cells. CELLULAR SIGNALLING, v. 46, p. 120-128, JUN 2018. (14/05214-1, 10/02272-0, 17/11540-7)

FERREIRA, SABRINA S.; NUNES, FERNANDA P. B.; CASAGRANDE, FELIPE B.; MARTINS, JOILSON O.. Insulin Modulates Cytokine Release, Collagen and Mucus Secretion in Lung Remodeling of Allergic Diabetic Mice. FRONTIERS IN IMMUNOLOGY, v. 8, JUN 9 2017. (14/05214-1, 12/06617-7, 10/02272-0)

TESSARO, FERNANDO H. G.; AYALA, THAIS S.; NOLASCO, EDUARDO L.; BELLA, LEONARDO M.; MARTINS, JOILSON O.. Insulin Influences LPS-Induced TNF-alpha and IL-6 Release Through Distinct Pathways in Mouse Macrophages from Different Compartments. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 42, n. 5, p. 2093-2104, 2017. (14/05214-1, 17/15625-7, 12/23998-4, 10/02272-0)

BELLA, LEONARDO M.; FIERI, ISIS; TESSARO, FERNANDO H. G.; NOLASCO, EDUARDO L.; NUNES, FERNANDA P. B.; FERREIRA, SABRINA S.; AZEVEDO, CAROLINA B.; MARTINS, JOILSON O.. Vitamin D Modulates Hematological Parameters and Cell Migration into Peritoneal and Pulmonary Cavities in Alloxan-Diabetic Mice. BIOMED RESEARCH INTERNATIONAL, v. 2017, p. 10-pg., 2017-01-01. (13/20904-1, 12/23998-4, 10/02272-0, 14/05214-1)

CASAGRANDE, FELIPE BECCARIA; FERREIRA, SABRINA DE SOUZA; BARBOSA NUNES, FERNANDA PEIXOTO; DAL'MAS ROMERA, LAVINIA MARIA; DOS SANTOS, SUELEN SILVANA; GALVAO TESSARO, FERNANDO HENRIQUE; KNOX DE SOUZA, PAULA REGINA; ALMEIDA, SANDRO ROGERIO; MARTINS, JOILSON OLIVEIRA. Insulin Modulates Paracoccidioides brasiliensis-Induced Inflammation by Restoring the Populations of NK Cells, Dendritic Cells, and B Lymphocytes in Lungs. JOURNAL OF DIABETES RESEARCH, v. 2018, p. 11-pg., 2018-01-01. (10/02272-0, 12/06617-7, 17/11540-7, 12/06652-7, 14/05214-1)

BARKER, CHRISTOPHER J.; TESSARO, FERNANDO HENRIQUE GALVAO; FERREIRA, SABRINA DE SOUZA; SIMAS, RAFAEL; AYALA, THAIS S.; KOHLER, MARTIN; RAJASEKARAN, SUBU SURENDRAN; MARTINS, JOILSON O.; DARE, ELISABETTA; BERGGREN, PER-OLOF. XPR1 Mediates the Pancreatic beta-Cell Phosphate Flush. Diabetes, v. 70, n. 1, p. 111-118, JAN 2021. (14/05214-1, 10/02272-0, 17/11540-7)

CASAGRANDE, FELIPE BECCARIA; FERREIRA, SABRINA DE SOUZA; BARBOSA NUNES, FERNANDA PEIXOTO; DAL'MAS ROMERA, LAVINIA MARIA; DOS SANTOS, SUELEN SILVANA; GALVAO TESSARO, FERNANDO HENRIQUE; KNOX DE SOUZA, PAULA REGINA; ALMEIDA, SANDRO ROGERIO; MARTINS, JOILSON OLIVEIRA. Insulin Modulates Paracoccidioides brasiliensis-Induced Inflammation by Restoring the Populations of NK Cells, Dendritic Cells, and B Lymphocytes in Lungs. JOURNAL OF DIABETES RESEARCH, 2018. (17/11540-7, 12/06652-7, 14/05214-1, 12/06617-7, 10/02272-0)

AYALA, THAIS SOPRANI; GALVAO TESSARO, FERNANDO HENRIQUE; JANNUZZI, GRASIELLE PEREIRA; BELLA, LEONARDO MENDES; FERREIRA, KAREN SPADARI; MARTINS, JOILSON O.. High Glucose Environments Interfere with Bone Marrow-Derived Macrophage Inflammatory Mediator Release, the TLR4 Pathway and Glucose Metabolism. SCIENTIFIC REPORTS, v. 9, AUG 7 2019. (14/05214-1, 17/11540-7)

GALVAO TESSARO, FERNANDO HENRIQUE; AYALA, THAIS SOPRANI; BELLA, LEONARDO MENDES; MARTINS, JOILSON OLIVEIRA. Macrophages from a type 1 diabetes mouse model present dysregulated P13K/AKT, ERK 1/2 and SAPK/JNK levels. Immunobiology, v. 225, n. 2, MAR 2020. (14/05214-1, 17/11540-7, 10/02272-0)

KNOX DE SOUZA, PAULA R.; FERREIRA, SABRINA S.; NUNES, FERNANDA P. B.; CASAGRANDE, FELIPE B.; TESSARO, FERNANDO H. G.; SILVA, MARIANA C. F.; MIRANDA COSTA CRUZ, JOSE WALBER; MAMIZUKA, ELSA M.; MARTINS, JOILSON O.. Cytokine and Adhesion Molecule Expression Induced by Different Strains of Staphylococcus aureus in Type 1 Diabetic Rats: Role of Insulin. FRONTIERS IN IMMUNOLOGY, v. 9, JAN 17 2019. (17/11540-7, 12/06652-7, 14/05214-1, 10/02272-0)

NOLASCO, EDUARDO L.; ZANONI, FERNANDO L.; NUNES, FERNANDA P. B.; FERREIRA, SABRINA S.; FREITAS, LUIZA A.; SILVA, MARIANA C. F.; MARTINS, JOILSON O.. Insulin Modulates Liver Function in a Type I Diabetes Rat Model. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 36, n. 4, p. 1467-1479, 2015. (14/05214-1, 10/02272-0)

RAJASEKARAN, SUBU SURENDRAN; ILLIES, CHRISTOPHER; SHEARS, STEPHEN B.; WANG, HUANCHEN; AYALA, THAIS S.; MARTINS, JOILSON O.; DARE, ELISABETTA; BERGGREN, PER-OLOF; BARKER, CHRISTOPHER J.. Protein kinase- and lipase inhibitors of inositide metabolism deplete IP7 indirectly in pancreatic beta-cells: Off-target effects on cellular bioenergetics and direct effects on IP6K activity. CELLULAR SIGNALLING, v. 42, p. 127-133, JAN 2018. (14/05214-1, 10/02272-0)

CASAGRANDE, FELIPE BECCARIA; FERREIRA, SABRINA DE SOUZA; ALHO DE SOUSA, EMANUELLA SARMENTO; TORRES GUIMARAES, JOAO PEDRO; DAL'MAS ROMERA, LAVINIA MARIA; GALVAO TESSARO, FERNANDO HENRIQUE; DE ALMEIDA, SANDRO ROGERIO; DE PAULA RODRIGUES, STEPHEN FERNANDES; MARTINS, JOILSON O.. Insulin Modulates Inflammatory Cytokine Release in Acute Stages and Augments Expression of Adhesion Molecules and Leukocytes in Lungs on Chronic Stages of Paracoccidioidomycosis. FRONTIERS IN IMMUNOLOGY, v. 11, NOV 18 2020. (17/11540-7, 14/05214-1)

FERREIRA, SABRINA S.; OLIVEIRA, MARIA A.; TSUJITA, MARISTELA; NUNES, FERNANDA P. B.; CASAGRANDE, FELIPE B.; GOMES, ELIANE; RUSSO, MOMTCHILO; TAVARES DE LIMA, WOTHAN; MARTINS, JOILSON O.. Insulin Modulates the Immune Cell Phenotype in Pulmonary Allergic Inflammation and Increases Pulmonary Resistance in Diabetic Mice. FRONTIERS IN IMMUNOLOGY, v. 11, FEB 11 2020. (14/05214-1, 17/11540-7)