FIG. 8.

Exogenous ATP increased glucose uptake in adult muscle fibers derived from control mice fed a normal-chow diet (NCD) and mice fed a high-fat diet (HFD). Proposed model for ATP-mediated glucose uptake. A: Fibers were stimulated with ATP and/or insulin at indicated concentrations, and 2-NBDG uptake was assayed. B: Adult fibers were isolated from mice fed NCD and HFD. 2-NBDG uptake was measured after insulin (100 nmol/L) or ATP (100 μmol/L) stimulation. Values are the mean ± SD. **P < 0.001 vs. basal; ††P < 0.001 with respect to basal HFD muscle fibers. C: In the proposed model, electrical stimulation induces the opening of an ATP extrusion pathway, potentially via pannexin 1 (PnX1) activated by a conformational change of the adjacent dihydropyridine receptor (DHPR). This ATP released to the extracellular medium induces an autocrine activation of P2Y receptors. ATP signals through the βγ subunits of a heterotrimeric G protein to activate PI3K-γ, Akt, AS160, and Rab8A, promoting GLUT4 exocytosis and reducing GLUT4 endocytosis. (A high-quality color representation of this figure is available in the online issue.)