Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes
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Aims/hypothesis Exercise enhances insulin-stimulated glucose transport in skeletal muscle through changes in signal transduction and gene expression. The aim of this study was to assess the impact of acute and short-term exercise training on whole-body insulin-mediated glucose disposal and signal transduction along the canonical insulin signalling cascade.Methods A euglycaemic-hyperinsulinaemic clamp, with vastus lateralis skeletal muscle biopsies, was performed at baseline and 16 h after an acute bout of exercise and short-term exercise training (7 days) in obese non-diabetic (n=7) and obese type 2 diabetic (n=8) subjects.Results Insulin-mediated glucose disposal was unchanged following acute exercise in both groups. Short-term exercise training increased insulin-mediated glucose disposal in obese type 2 diabetic (p<0.05), but not in obese non-diabetic subjects. Insulin activation of (1) IRS1, (2) IRS2, (3) phosphotyrosine-associated phosphatidylinositol-3 kinase activity and (4) the substrate of phosphorylated Akt, AS160, a functional Rab GTPase activating protein important for GLUT4 (now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) translocation, was unchanged after acute or chronic exercise in either group. GLUT4 protein content was increased in obese type 2 diabetic subjects (p<0.05), but not in obese non-diabetic subjects following chronic exercise.Conclusions/interpretation Exercise training increased whole-body insulin-mediated glucose disposal in obese type 2 diabetic patients. These changes were independent of functional alterations in the insulin-signalling cascade and related to increased GLUT4 protein content.
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The acute effects of a recent bout of exercise account for most of the improvements in insulin action, with most individuals experiencing a decrease in their blood glucose levels during mild- and moderate-intensity exercise and for 2-72 h afterward.
“The acute effects of a recent bout of exercise account for most of the improvements in insulin action, with most individuals experiencing a decrease in their BG levels during mild- and moderate-intensity exercise and for 2–72 h afterward ( 24 , 83 , 204 ).”
From Exercise and Type 2 Diabetes (2010) · cites this paper as [204]
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Experimental — accuracy not yet measuredSkeletal muscle responds to contraction or exercise with a rapid insulin-independent increase in glucose uptake during exercise and a transient insulin-stimulated pathway following exercise.
“Skeletal muscle responds to contraction or exercise with a rapid insulin-independent increase in glucose uptake during exercise and a transient insulin-stimulated pathway following exercise 7-11.”
From Effect of exercise training on insulin-stimulated glucose disposal: A systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [9]
The Introduction says muscle contractions during acute exercise enhance glucose transport, and the Discussion reports enhanced insulin-mediated glucose disposal for up to two days after exercise in healthy young subjects. Our copy does not establish that uptake during exercise is rapid and insulin-independent; its explicit discussion of insulin-independent regulation concerns the period after exercise. It also reports no improvement in insulin-mediated disposal 16 hours after acute exercise in the obese and type 2 diabetic subjects studied (Introduction and Discussion; pages unavailable). (LLM, conf=0.84)
Experimental — accuracy not yet measuredTraining can enhance the responsiveness of skeletal muscles to insulin with increased expression and/or activity of proteins involved in glucose metabolism and insulin signaling.
“Training can enhance the responsiveness of skeletal muscles to insulin with increased expression and/or activity of proteins involved in glucose metabolism and insulin signaling ( 39 , 110 , 204 , 270 ).”
From Exercise and Type 2 Diabetes (2010) · cites this paper as [204]
The Discussion (page unavailable in our copy) reports that short-term training increased insulin-mediated glucose disposal in obese patients with type 2 diabetes and relates the improvement to increased GLUT4 protein content. It also says the improvement was independent of changes in several components of the canonical insulin-signalling cascade, so the claim’s implication that signalling-protein activity increased in these patients is not supported. (LLM, conf=0.88)
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References 51 · Cited by 226
- Authors
- O’Gorman, D. J., Karlsson, H. K. R., McQuaid, S., Yousif, O., Rahman, Y., Gasparro, D., Glund, S., Chibalin, A. V., Zierath, J. R., & Nolan, J. J.
- Affiliations
- Trinity College Dublin (IE)
- Karolinska Institutet (SE)
- Corresponding author
- Nolan, J. J.
- ORCID
- Venue
- Diabetologia
- Published
- 2006-09-26
- Volume
- 49
- Issue
- 12
- Pages
- 2983-2992
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2032370338
- Semantic Scholar
- 1e58b8d934a8506f6507d7c801a5f8297df62b5f
- Cited by
- 226
- References
- 51
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 17 · 2020: 12 · 2019: 17 · 2018: 13 · 2017: 10 · 2016: 14 · 2015: 7 · 2014: 14 · 2013: 19 · 2012: 10
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vetenskapsrådet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Physiology › Physical Activity and Health
- Keywords
- exercise training, type 2 diabetes, insulin-stimulated glucose disposal, GLUT4, SLC2A4, insulin signaling, IRS-1, insulin receptor substrate 2, PI3K/Akt signaling, AS160, skeletal muscle glucose transport, obesity, hyperinsulinemic-euglycemic clamp
- MeSH terms
- Biopsy, Blood Glucose, Blood Pressure, Diabetes Mellitus, Type 2, Diet, Diabetic, Exercise Test, Female, Humans, Insulin, Male, Middle Aged, Obesity, Glucose Clamp Technique, Exercise, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Glucose Transporter Type 4
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