Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle

Masaaki Sato, Nodi Dehvari, Anette Oberg, Olof S Dallner, Anna L Sandstrom, Jessica M Olsen, Robert I Csikasz, Roger James Summers, Dana Sabine Hutchinson, Tore Bengtsson

Research output: Contribution to journalArticleResearchpeer-review

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 ?2-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.
Original languageEnglish
Pages (from-to)4115 - 4129
Number of pages15
JournalDiabetes
Volume63
Issue number12
DOIs
Publication statusPublished - 2014

Cite this

Sato, M., Dehvari, N., Oberg, A., Dallner, O. S., Sandstrom, A. L., Olsen, J. M., ... Bengtsson, T. (2014). Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle. Diabetes, 63(12), 4115 - 4129. https://doi.org/10.2337/db13-1860
Sato, Masaaki ; Dehvari, Nodi ; Oberg, Anette ; Dallner, Olof S ; Sandstrom, Anna L ; Olsen, Jessica M ; Csikasz, Robert I ; Summers, Roger James ; Hutchinson, Dana Sabine ; Bengtsson, Tore. / Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle. In: Diabetes. 2014 ; Vol. 63, No. 12. pp. 4115 - 4129.
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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 ?2-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.",
author = "Masaaki Sato and Nodi Dehvari and Anette Oberg and Dallner, {Olof S} and Sandstrom, {Anna L} and Olsen, {Jessica M} and Csikasz, {Robert I} and Summers, {Roger James} and Hutchinson, {Dana Sabine} and Tore Bengtsson",
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Improving type 2 diabetes through a distinct adrenergic signaling pathway involving mTORC2 that mediates glucose uptake in skeletal muscle. / Sato, Masaaki; Dehvari, Nodi; Oberg, Anette; Dallner, Olof S; Sandstrom, Anna L; Olsen, Jessica M; Csikasz, Robert I; Summers, Roger James; Hutchinson, Dana Sabine; Bengtsson, Tore.

In: Diabetes, Vol. 63, No. 12, 2014, p. 4115 - 4129.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Sandstrom, Anna L

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