Acute metformin therapy confers cardioprotection against myocardial infarction via AMPK-eNOS-mediated signaling.
Diabetes
; 57(3): 696-705, 2008 Mar.
Article
en En
| MEDLINE
| ID: mdl-18083782
ABSTRACT
OBJECTIVE:
Clinical studies have reported that metformin reduces cardiovascular end points of type 2 diabetic subjects by actions that cannot solely be attributed to glucose-lowering effects. The therapeutic effects of metformin have been reported to be mediated by its activation of AMP-activated protein kinase (AMPK), a metabolite sensing protein kinase whose activation following myocardial ischemia has been suggested to be an endogenous protective signaling mechanism. We investigated the potential cardioprotective effects of a single, low-dose metformin treatment (i.e., 286-fold less than the maximum antihyperglycemic dose) in a murine model of myocardial ischemia-reperfusion (I/R) injury. RESEARCH DESIGN ANDMETHODS:
Nondiabetic and diabetic (db/db) mice were subjected to transient myocardial ischemia for a period of 30 min followed by reperfusion. Metformin (125 microg/kg) or vehicle (saline) was administered either before ischemia or at the time of reperfusion.RESULTS:
Administration of metformin before ischemia or at reperfusion decreased myocardial injury in both nondiabetic and diabetic mice. Importantly, metformin did not alter blood glucose levels. During early reperfusion, treatment with metformin augmented I/R-induced AMPK activation and significantly increased endothelial nitric oxide (eNOS) phosphorylation at residue serine 1177.CONCLUSIONS:
These findings provide important information that myocardial AMPK activation by metformin following I/R sets into motion events, including eNOS activation, which ultimately lead to cardioprotection.
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Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Adenilato Quinasa
/
Proteínas Serina-Treonina Quinasas
/
Diabetes Mellitus
/
Óxido Nítrico Sintasa de Tipo III
/
Metformina
/
Complejos Multienzimáticos
/
Infarto del Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Diabetes
Año:
2008
Tipo del documento:
Article
País de afiliación:
Estados Unidos