Metabolites as regulators of insulin sensitivity and metabolism.
Nat Rev Mol Cell Biol
; 19(10): 654-672, 2018 10.
Article
en En
| MEDLINE
| ID: mdl-30104701
ABSTRACT
The cause of insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is not limited to impaired insulin signalling but also involves the complex interplay of multiple metabolic pathways. The analysis of large data sets generated by metabolomics and lipidomics has shed new light on the roles of metabolites such as lipids, amino acids and bile acids in modulating insulin sensitivity. Metabolites can regulate insulin sensitivity directly by modulating components of the insulin signalling pathway, such as insulin receptor substrates (IRSs) and AKT, and indirectly by altering the flux of substrates through multiple metabolic pathways, including lipogenesis, lipid oxidation, protein synthesis and degradation and hepatic gluconeogenesis. Moreover, the post-translational modification of proteins by metabolites and lipids, including acetylation and palmitoylation, can alter protein function. Furthermore, the role of the microbiota in regulating substrate metabolism and insulin sensitivity is unfolding. In this Review, we discuss the emerging roles of metabolites in the pathogenesis of insulin resistance and T2DM. A comprehensive understanding of the metabolic adaptations involved in insulin resistance may enable the identification of novel targets for improving insulin sensitivity and preventing, and treating, T2DM.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Diabetes Mellitus Tipo 2
/
Glucosa
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Rev Mol Cell Biol
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos