Acute treadmill exercise discriminately improves the skeletal muscle insulin-stimulated growth signaling responses in mice lacking REDD1

Cory M. Dungan, Bradley S. Gordon, David L. Williamson, IV

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere14011
JournalPhysiological reports
Volume7
Issue number4
DOIs
StatePublished - Feb 1 2019

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DNA Damage
Skeletal Muscle
Exercise
Insulin
Knockout Mice
Growth
AMP-Activated Protein Kinases
Phosphorylation
Insulin Resistance
Muscles
mechanistic target of rapamycin complex 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

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title = "Acute treadmill exercise discriminately improves the skeletal muscle insulin-stimulated growth signaling responses in mice lacking REDD1",
abstract = "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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Acute treadmill exercise discriminately improves the skeletal muscle insulin-stimulated growth signaling responses in mice lacking REDD1. / Dungan, Cory M.; Gordon, Bradley S.; Williamson, IV, David L.

In: Physiological reports, Vol. 7, No. 4, e14011, 01.02.2019.

Research output: Contribution to journalArticle

TY - JOUR

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