Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle.
Diabetes
; 63(12): 4115-29, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25008179
ABSTRACT
There is an increasing worldwide epidemic of type 2 diabetes that poses major health problems. We have identified a novel physiological system that increases glucose uptake in skeletal muscle but not in white adipocytes. Activation of this system improves glucose tolerance in Goto-Kakizaki rats or mice fed a high-fat diet, which are established models for type 2 diabetes. The pathway involves activation of ß2-adrenoceptors that increase cAMP levels and activate cAMP-dependent protein kinase, which phosphorylates mammalian target of rapamycin complex 2 (mTORC2) at S2481. The active mTORC2 causes translocation of GLUT4 to the plasma membrane and glucose uptake without the involvement of Akt or AS160. Stimulation of glucose uptake into skeletal muscle after activation of the sympathetic nervous system is likely to be of high physiological relevance because mTORC2 activation was observed at the cellular, tissue, and whole-animal level in rodent and human systems. This signaling pathway provides new opportunities for the treatment of type 2 diabetes.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicemia
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Receptores Adrenérgicos beta 2
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Músculo Esquelético
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Complexos Multiproteicos
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Diabetes Mellitus Experimental
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Diabetes Mellitus Tipo 2
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Transportador de Glucose Tipo 4
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Serina-Treonina Quinases TOR
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2014
Tipo de documento:
Article