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Cited by 62Metabolism, Diabetes, and CancerCellular transport and secretionPancreatic function and diabetes

Kinetics of GLUT4 Trafficking in Rat and Human Skeletal Muscle

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Karlsson, Håkan K.R., Chibalin, Alexander V., Koistinen, Heikki A., Yang, Jing, Koumanov, Francoise, Wallberg-Henriksson, Harriet, Zierath, Juleen R., Holman, Geoffrey D.·2009·Diabetes
DOI 10.2337/db08-1539PMC PMC2661600
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Abstract

OBJECTIVE: In skeletal muscle, insulin stimulates glucose transport activity three- to fourfold, and a large part of this stimulation is associated with a net translocation of GLUT4 from an intracellular compartment to the cell surface. We examined the extent to which insulin or the AMP-activated protein kinase activator AICAR can lead to a stimulation of the exocytosis limb of the GLUT4 translocation pathway and thereby account for the net increase in glucose transport activity. RESEARCH DESIGN AND METHODS: Using a biotinylated photoaffinity label, we tagged endogenous GLUT4 and studied the kinetics of exocytosis of the tagged protein in rat and human skeletal muscle in response to insulin or AICAR. Isolated epitrochlearis muscles were obtained from male Wistar rats. Vastus lateralis skeletal muscle strips were prepared from open muscle biopsies obtained from six healthy men (age 39 ± 11 years and BMI 25.8 ± 0.8 kg/m2). RESULTS: In rat epitrochlearis muscle, insulin exposure leads to a sixfold stimulation of the GLUT4 exocytosis rate (with basal and insulin-stimulated rate constants of 0.010 and 0.067 min−1, respectively). In human vastus lateralis muscle, insulin stimulates GLUT4 translocation by a similar sixfold increase in the exocytosis rate constant (with basal and insulin-stimulated rate constants of 0.011 and 0.075 min−1, respectively). In contrast, AICAR treatment does not markedly increase exocytosis in either rat or human muscle. CONCLUSIONS: Insulin stimulation of the GLUT4 exocytosis rate constant is sufficient to account for most of the observed increase in glucose transport activity in rat and human muscle.

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  • Kinetic rates involved in GLUT translocation, including the effects of insulin and glucocorticoids, were estimated from prior studies.

    “the kinetic rates involved in the translocation of GLUT transporters, including the effects of insulin and glucocorticoids, were estimated from ( 27, 34, 46 );”

    From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [46]

    The Results section (page not available in our copy) reports basal and insulin-stimulated GLUT4 exocytosis rate constants in rat and human skeletal muscle. The paper supports using it for insulin-related trafficking rates, but the passages do not address glucocorticoid effects. (LLM, conf=0.87)

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Authors
Karlsson, H. K. R., Chibalin, A. V., Koistinen, H. A., Yang, J., Koumanov, F., Wallberg-Henriksson, H., Zierath, J. R., & Holman, G. D.
Affiliations
  • Karolinska Institutet (SE)
  • Helsinki University Hospital (FI)
  • University of Bath (GB)
  • Department of Biology and Biochemistry, University of Bath, Bath, U.K.;
  • Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Corresponding author
Holman, Geoffrey D.
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2009-02-02
Volume
58
Issue
4
Pages
847-854
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db08-1539
PMC
PMC2661600
OpenAlex
W2153446853
Cited by
62
References
47
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 7 · 2013: 4 · 2012: 2
FWCI
2.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust
  • European Foundation for the Study of Diabetes
  • Suomen Kulttuurirahasto
  • Knut och Alice Wallenbergs Stiftelse
  • Novo Nordisk
  • Vetenskapsrådet
  • Diabetestutkimussäätiö
  • Medical 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 › Cellular transport and secretion
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Keywords
GLUT4, insulin signaling, skeletal muscle, glucose transport, GLUT4 translocation, exocytosis kinetics, AMPK, AICAR, epitrochlearis muscle, vastus lateralis
MeSH terms
Adult, Animals, Biopsy, Cell Membrane, Exocytosis, Glucose, Humans, Insulin, Kinetics, Male, Middle Aged, Phosphoproteins, Muscle, Skeletal, Protein Transport, Glucose Transporter Type 4, Rats

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