A loss of the regulated in development and DNA damage 1 (REDD1) hyperactivates mechanistic Target of Rapamycin Complex 1 (mTORC1) reducing insulin‐stimulated insulin signaling, which could provide insight into mechanisms of insulin resistance. Although aerobic exercise acutely inhibits mTORC1 signaling, improvements in insulin‐stimulated signaling are exhibited. The goal of this study was to determine if a single bout of treadmill exercise was sufficient to improve insulin signaling in mice lacking REDD1. REDD1 wildtype (WT) and REDD1 knockout (KO) mice were acutely exercised on a treadmill (30 min, 20 m/min, 5% grade). A within animal noninsulin‐to‐insulin‐stimulated percent change in skeletal muscle insulin‐stimulated kinases (IRS‐1, ERK1/2, Akt), growth signaling activation (4E‐BP1, S6K1), and markers of growth repression (REDD1, AMPK, FOXO1/3A) was examined, following no exercise control or an acute bout of exercise. Unlike REDD1 KO mice, REDD1 WT mice exhibited an increase (P < 0.05) in REDD1 following treadmill exercise. However, both REDD1 WT and KO mice exhibited an increase (P < 0.05) AMPK phosphorylation, and a subsequent reduction (P < 0.05) in mTORC1 signaling after the exercise bout versus nonexercising WT or KO mice. Exercise increased (P < 0.05) the noninsulin‐to‐insulin‐stimulated percent change phosphorylation of mTORC1, ERK1/2, IRS‐1, and Akt on S473 in REDD1 KO mice when compared to nonexercised KO mice. However, there was no change in the noninsulin‐to‐insulin‐stimulated percent change activation of Akt on T308 and FOXO1/3A in the KO when compared to WT or KO mouse muscle after exercise. Our data show that a bout of treadmill exercise discriminately improves insulin‐stimulated signaling in the absence of REDD1.
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This research was supported by University at Buffalo, SUNY and Penn State Harrisburg (DLW) and the Mark Diamond Research Fund (CMD).
Dungan, Cory M.; Gordon, Bradley S.; and Williamson, David L, "Acute Treadmill Exercise Discriminately Improves the Skeletal Muscle Insulin-Stimulated Growth Signaling Responses in Mice Lacking REDD1" (2019). Physical Therapy Faculty Publications. 109.