Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle
| Autor: | Olof S. Dallner, Tore Bengtsson, Nodi Dehvari, Roger J. Summers, Robert I. Csikasz, Dana S. Hutchinson, Masaaki Sato, Anna L. Sandström, Jessica M. Olsen, Anette I. Öberg |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
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 |
| Zdroj: | Diabetes. 63(12) |
| ISSN: | 1939-327X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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