Metabolic reprogramming of macrophages in the context of type 2 diabetes

• Published in: European journal of medical research Vol. 29; no. 1; pp. 497 - 10
• Main Authors: Witcoski Junior, Leonel, de Lima, Jordana Dinorá, Somensi, Amanda Girardi, de Souza Santos, Lucas Brito, Paschoal, Giulia Leonel, Uada, Thalita Suemy, Bastos, Thais Sibioni Berti, de Paula, André Guilherme Portela, Dos Santos Luz, Rebeca Bosso, Czaikovski, Andressa Pacheco, Davanso, Mariana Rodrigues, Braga, Tarcio Teodoro
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 16-10-2024; BioMed Central; BMC
• Subjects: Animals; Care and treatment; Cellular Reprogramming; Cytokines; Dextrose; Diabetes Mellitus, Type 2 - metabolism; Diagnosis; Epigenetic inheritance; Epigenetic modifications; Evaluation; Fatty acids; Glucose; Glucose metabolism; Health aspects; Humans; Hyperglycemia; Immunometabolism; Inflammation; Inflammation - metabolism; Insulin; Insulin Resistance; Macrophage; Macrophages; Macrophages - immunology; Macrophages - metabolism; Metabolic regulation; Metabolic Reprogramming; Nitric oxide; Physiological aspects; Review; T2D; Type 2 diabetes; Brazil; Immunometabolism; Epigenetic modifications; T2D; Macrophage
• ISSN: 2047-783X; 0949-2321; 2047-783X
• DOI: 10.1186/s40001-024-02069-y

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, influencing both the development and progression of insulin resistance. These innate immune cells respond to inflammatory stimuli and reprogram their metabolism, directly impacting the pathophysiology of T2D. Macrophages are highly plastic and can adopt either pro-inflammatory or pro-resolutive phenotypic profiles. In T2D, pro-inflammatory macrophages, which rely on glycolysis, exacerbate insulin resistance through increased production of pro-inflammatory cytokines and nitric oxide. In contrast, pro-resolutive macrophages, which prioritize fatty acid metabolism, have different effects on glucose homeostasis. Metaflammation, a chronic low-grade inflammation, is induced by pro-inflammatory macrophages and significantly 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 inflammatory responses and metabolic reprogramming influence insulin resistance and the disease's pathophysiology. The review seeks to deepen the understanding of the biochemical and metabolic mechanisms involved, offering broader insights into the impact on the quality of life for millions of patients worldwide.