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https://www.arca.fiocruz.br/handle/icict/67760
METABOLIC REPROGRAMMING OF MACROPHAGES IN THE CONTEXT OF TYPE 2 DIABETES
Author
Witcoski, Leonel Junior
Lima, Jordana Dinorá
Somensi, Amanda Girardi
Santos, Lucas Brito de Souza
Paschoal, Giulia Leonel
Uada, Thalita Suemy
Bastos, Thais Sibioni Berti
Paula, André Guilherme Portela
Luz, Rebeca Bosso Dos Santos
Czaikovski, Andressa Pacheco
Davanso, Mariana Rodrigues
Braga, Tarcio Teodoro
Lima, Jordana Dinorá
Somensi, Amanda Girardi
Santos, Lucas Brito de Souza
Paschoal, Giulia Leonel
Uada, Thalita Suemy
Bastos, Thais Sibioni Berti
Paula, André Guilherme Portela
Luz, Rebeca Bosso Dos Santos
Czaikovski, Andressa Pacheco
Davanso, Mariana Rodrigues
Braga, Tarcio Teodoro
Affilliation
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Genetics. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Pharmacology. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Virologia Molecular. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Pharmacology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Tuiuti University of Paraná. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Genetics. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Pharmacology. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Virologia Molecular. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Pharmacology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Tuiuti University of Paraná. Curitiba, PR, Brasil.
Federal University of Paraná. Department of Basic Pathology. Curitiba, PR, Brasil.
Abstract
Type 2 diabetes (T2D) is associated with insulin resistance and progressive dysfunction of β-pancreatic cells, leading to persistent hyperglycemia. Macrophages play a crucial role in this context, infuencing both the development and progression of insulin resistance. These innate immune cells respond to infammatory stimuli and reprogram their metabolism, directly impacting the pathophysiology of T2D. Macrophages are highly plastic and can adopt either pro-infammatory or pro-resolutive phenotypic profles. In T2D, pro-infammatory macrophages, which rely on glycolysis, exacerbate insulin resistance through increased production of pro-infammatory cytokines and nitric oxide. In contrast, pro-resolutive macrophages, which prioritize fatty acid metabolism, have diferent efects on glucose homeostasis. Metafammation, a chronic low-grade infammation, is induced by pro-infammatory macrophages and signifcantly contributes to the progression of T2D, creating an environment conducive to metabolic dysfunction. This review aims to clarify the contribution of macrophages to the progression of T2D by detailing how their infammatory responses and metabolic reprogramming infuence insulin resistance and the disease’s pathophysiology. The review seeks to deepen the understanding of the biochemical and metabolic mechanisms involved, ofering broader insights into the impact on the quality of life for millions of patients worldwide.
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