Your browser doesn't support javascript.
loading
MCT4-dependent lactate transport: a novel mechanism for cardiac energy metabolism injury and inflammation in type 2 diabetes mellitus.
Ma, Xiu Mei; Geng, Kang; Wang, Peng; Jiang, Zongzhe; Law, Betty Yuen-Kwan; Xu, Yong.
Afiliación
  • Ma XM; Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macau, People's Republic of China.
  • Geng K; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, 999078, Macau, People's Republic of China.
  • Wang P; Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, 646000, Sichuan, People's Republic of China.
  • Jiang Z; Sichuan Clinical Research Center for Nephropathy, Luzhou, 646000, Sichuan, People's Republic of China.
  • Law BY; Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, 646000, Sichuan, People's Republic of China.
  • Xu Y; Sichuan Clinical Research Center for Nephropathy, Luzhou, 646000, Sichuan, People's Republic of China.
Cardiovasc Diabetol ; 23(1): 96, 2024 Mar 14.
Article en En | MEDLINE | ID: mdl-38486199
ABSTRACT
Diabetic cardiomyopathy (DCM) is a major contributor to mortality in diabetic patients, characterized by a multifaceted pathogenesis and limited therapeutic options. While lactate, a byproduct of glycolysis, is known to be significantly elevated in type 2 diabetes, its specific role in DCM remains uncertain. This study reveals an abnormal upregulation of monocarboxylate transporter 4 (MCT4) on the plasma membrane of cardiomyocytes in type 2 diabetes, leading to excessive lactate efflux from these cells. The disruption in lactate transport homeostasis perturbs the intracellular lactate-pyruvate balance in cardiomyocytes, resulting in oxidative stress and inflammatory responses that exacerbate myocardial damage. Additionally, our findings suggest increased lactate efflux augments histone H4K12 lactylation in macrophages, facilitating inflammatory infiltration within the microenvironment. In vivo experiments have demonstrated that inhibiting MCT4 effectively alleviates myocardial oxidative stress and pathological damage, reduces inflammatory macrophage infiltration, and enhances cardiac function in type 2 diabetic mice. Furthermore, a clinical prediction model has been established, demonstrating a notable association between peripheral blood lactate levels and diastolic dysfunction in individuals with type 2 diabetes. This underscores the potential of lactate as a prognostic biomarker for DCM. Ultimately, our findings highlight the pivotal involvement of MCT4 in the dysregulation of cardiac energy metabolism and macrophage-mediated inflammation in type 2 diabetes. These insights offer novel perspectives on the pathogenesis of DCM and pave the way for the development of targeted therapeutic strategies against this debilitating condition.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 2 / Cardiomiopatías Diabéticas Límite: Animals / Humans Idioma: En Revista: Cardiovasc Diabetol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / ENDOCRINOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 2 / Cardiomiopatías Diabéticas Límite: Animals / Humans Idioma: En Revista: Cardiovasc Diabetol Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / ENDOCRINOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido