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Methazolamide Attenuates the Development of Diabetic Cardiomyopathy by Promoting ß-Catenin Degradation in Type 1 Diabetic Mice.
Chen, Xiaoqing; Li, Yilang; Yuan, Xun; Yuan, Wenchang; Li, Conglin; Zeng, Yue; Lian, Yuling; Qiu, Xiaoxia; Qin, Yuan; Zhang, Guiping; Liu, Xiawen; Luo, Chengfeng; Luo, Jian-Dong; Hou, Ning.
Afiliación
  • Chen X; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Li Y; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Yuan X; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Yuan W; Guangzhou Key Laboratory for Clinical Rapid Diagnosis and Early Warning of Infectious Diseases, KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
  • Li C; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Zeng Y; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Lian Y; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Qiu X; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Qin Y; Zhujiang Hospital of Southern Medical University, Guangzhou, People's Republic of China.
  • Zhang G; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Liu X; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Luo C; Key Laboratory of Molecular Target and Clinical Pharmacology and the State and NMPA Key Laboratory, School of Pharmaceutical Sciences and The Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Luo JD; Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
  • Hou N; Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, People's Republic of China.
Diabetes ; 71(4): 795-811, 2022 04 01.
Article en En | MEDLINE | ID: mdl-35043173
Methazolamide (MTZ), a carbonic anhydrase inhibitor, has been shown to inhibit cardiomyocyte hypertrophy and exert a hypoglycemic effect in patients with type 2 diabetes and diabetic db/db mice. However, whether MTZ has a cardioprotective effect in the setting of diabetic cardiomyopathy is not clear. We investigated the effects of MTZ in a mouse model of streptozotocin-induced type 1 diabetes mellitus (T1DM). Diabetic mice received MTZ by intragastric gavage (10, 25, or 50 mg/kg, daily for 16 weeks). In the diabetic group, MTZ significantly reduced both random and fasting blood glucose levels and improved glucose tolerance in a dose-dependent manner. MTZ ameliorated T1DM-induced changes in cardiac morphology and dysfunction. Mechanistic analysis revealed that MTZ blunted T1DM-induced enhanced expression of ß-catenin. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) and adult mouse cardiomyocytes treated with high glucose or Wnt3a (a ß-catenin activator). There was no significant change in ß-catenin mRNA levels in cardiac tissues or NRCMs. MTZ-mediated ß-catenin downregulation was recovered by MG132, a proteasome inhibitor. Immunoprecipitation and immunofluorescence analyses showed augmentation of AXIN1-ß-catenin interaction by MTZ in T1DM hearts and in NRCMs treated with Wnt3a; thus, MTZ may potentiate AXIN1-ß-catenin linkage to increase ß-catenin degradation. Overall, MTZ may alleviate cardiac hypertrophy by mediating AXIN1-ß-catenin interaction to promote degradation and inhibition of ß-catenin activity. These findings may help inform novel therapeutic strategy to prevent heart failure in patients with diabetes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 1 / Diabetes Mellitus Tipo 2 / Cardiomiopatías Diabéticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Diabetes Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus Experimental / Diabetes Mellitus Tipo 1 / Diabetes Mellitus Tipo 2 / Cardiomiopatías Diabéticas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Diabetes Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos