The effect of exercise and insulin on AS160 phosphorylation and 14-3-3 binding capacity in human skeletal muscle
Abstract
AS160 is an Akt substrate of 160 kDa implicated in the regulation of both insulin- and contraction-mediated GLUT4 translocation and glucose uptake. The effects of aerobic exercise and subsequent insulin stimulation on AS160 phosphorylation and the binding capacity of 14-3-3, a novel protein involved in the dissociation of AS160 from GLUT4 vesicles, in human skeletal muscle are unknown. Hyperinsulinemic-euglycemic clamps were performed on seven men at rest and immediately and 3 h after a single bout of cycling exercise. Skeletal muscle biopsies were taken before and after the clamps. The insulin sensitivity index calculated during the final 30 min of the clamp was 8.0 +/- 0.8, 9.1 +/- 0.5, and 9.2 +/- 0.8 for the rest, postexercise, and 3-h postexercise trials, respectively. AS160 phosphorylation increased immediately after exercise and remained elevated 3 h after exercise. In contrast, the 14-3-3 binding capacity of AS160 and phosphorylation of Akt and AMP-activated protein kinase were only increased immediately after exercise. Insulin increased AS160 phosphorylation and 14-3-3 binding capacity and insulin receptor substrate-1 and Akt phosphorylation, but the response to insulin was not enhanced by prior exercise. In conclusion, the 14-3-3 binding capacity of AS160 is increased immediately after acute exercise in human skeletal muscle, but this is not maintained 3 h after exercise completion despite sustained AS160 phosphorylation. Insulin increases AS160 phosphorylation and 14-3-3 binding capacity, but prior exercise does not appear to enhance the response to insulin.
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Exercise-induced AMPK is thought to phosphorylate and inhibit the Rab-GAP proteins TBC1D1/TBC1D4.
“In addition to this event exercise induced AMPK is also thought to phosphorylate and inhibit the Rab-GAP proteins TBC1D1/TBC1D4 [16][17][18].”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [17]
3 hours of cycling increased 14-3-3 binding to TBC1D4 immediately following exercise, but this had returned to baseline despite maintained TBC1D4 phosphorylation 3 hours postexercise.
“Similarly, Howlett et al. [124] found that although 3 hours of cycling increased 14-3-3 binding to TBC1D4 immediately following exercise, this had returned to baseline despite maintained TBC1D4 phosphorylation 3 hours postexercise.”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [124]
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- Authors
- Howlett, K. F., Mathews, A., Garnham, A., & Sakamoto, K.
- Affiliations
- Deakin University (AU)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2008-02
- Volume
- 294
- Issue
- 2
- Pages
- E401-E407
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2027893952
- Cited by
- 47
- References
- 37
- Citations by year
- 2023: 1 · 2022: 4 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 5
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Funders
- Medical Research Council
- Australian Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- AS160, 14-3-3 binding, insulin signaling, skeletal muscle, aerobic exercise, GLUT4 translocation, glucose uptake, Akt phosphorylation, AMPK, IRS-1, insulin sensitivity
- MeSH terms
- Acetyl-CoA Carboxylase, Adult, Humans, Insulin, Male, Muscle Proteins, Phosphorylation, Protein Binding, Blotting, Western, Glucose Clamp Technique, Signal Transduction, Exercise, Muscle, Skeletal, GTPase-Activating Proteins, Immunoprecipitation, Adaptor Proteins, Signal Transducing, 14-3-3 Proteins, Oncogene Protein v-akt, Glucose Transporter Type 4, Insulin Receptor Substrate Proteins
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