Type 2 diabetes is an increasing worldwide epidemic 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 PKA that 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 following activation of the sympathetic nervous system is likely to be of high physiological relevance since mTOR complex 2 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.
- Received December 9, 2013.
- Accepted June 29, 2014.
- © 2014 by the American Diabetes Association.
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