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Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle
- Source :
- Diabetes. 63(12)
- Publication Year :
- 2014
-
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 β2-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.
- Subjects :
- Blood Glucose
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Glucose uptake
Type 2 diabetes
Mechanistic Target of Rapamycin Complex 2
Biology
Diet, High-Fat
mTORC2
Diabetes Mellitus, Experimental
Rats, Sprague-Dawley
Mice
Internal medicine
Internal Medicine
medicine
Animals
Phosphorylation
Muscle, Skeletal
Protein kinase B
Cells, Cultured
Mice, Knockout
Glucose Transporter Type 4
TOR Serine-Threonine Kinases
Skeletal muscle
Glucose Tolerance Test
medicine.disease
Cyclic AMP-Dependent Protein Kinases
Rats
Mice, Inbred C57BL
Endocrinology
medicine.anatomical_structure
Diabetes Mellitus, Type 2
Multiprotein Complexes
biology.protein
Receptors, Adrenergic, beta-2
Signal transduction
Proto-Oncogene Proteins c-akt
GLUT4
Signal Transduction
Subjects
Details
- ISSN :
- 1939327X
- Volume :
- 63
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....b6be94ab116c7dd361f61873877a8431