Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis.
Proc Natl Acad Sci U S A
; 119(10): e2122287119, 2022 03 08.
Article
en En
| MEDLINE
| ID: mdl-35238637
ABSTRACT
SignificanceMetformin is the most commonly prescribed drug for the treatment of type 2 diabetes mellitus, yet the mechanism by which it lowers plasma glucose concentrations has remained elusive. Most studies to date have attributed metformin's glucose-lowering effects to inhibition of complex I activity. Contrary to this hypothesis, we show that inhibition of complex I activity in vitro and in vivo does not reduce plasma glucose concentrations or inhibit hepatic gluconeogenesis. We go on to show that metformin, and the related guanides/biguanides, phenformin and galegine, inhibit complex IV activity at clinically relevant concentrations, which, in turn, results in inhibition of glycerol-3-phosphate dehydrogenase activity, increased cytosolic redox, and selective inhibition of glycerol-derived hepatic gluconeogenesis both in vitro and in vivo.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fenformina
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Complejo IV de Transporte de Electrones
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Gluconeogénesis
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Guanidinas
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Hipoglucemiantes
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Metformina
Límite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2022
Tipo del documento:
Article