Cited by 774Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismMuscle metabolism and nutrition

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Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport

Hayashi, T., Hirshman, M. F., Kurth, E. J., Winder, W. W., Goodyear, L. J.·1998·Diabetes

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Abstract

The intracellular signaling proteins that lead to exercise-stimulated glucose transport in skeletal muscle have not been identified, although it is clear that there are separate signaling mechanisms for exercise- and insulin-stimulated glucose transport. We have hypothesized that the 5'AMP-activated protein kinase (AMPK) functions as a signaling intermediary in exercise-stimulated glucose uptake. This hypothesis was based on recent studies showing the following: 1) muscle contraction increases AMPK activity and 2) perfusion of rat hindlimb skeletal muscles with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a compound that results in increased AMPK activity, increased insulin-stimulated glucose uptake. In the current study, isolated rat epitrochlearis muscles were treated to contract in vitro (via electrical stimulation for 10 min) and/or incubated in the absence or presence of AICAR (2 mmol/l), insulin (1 micromol/l), or wortmannin (100 nmol/l). Both contraction and AICAR significantly increased AMPK activity, while the enzyme was not activated by insulin. AICAR, contraction, and insulin all increased 3-O-methylglucose (3MG) transport by threefold to fivefold above basal. The phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin completely blocked insulin-stimulated transport, but did not inhibit AICAR- or contraction-stimulated transport. The increase in glucose transport with the combination of maximal AICAR plus maximal insulin treatments was partially additive, suggesting that these stimuli increase glucose transport by different mechanisms. In contrast, there was no additive effect on glucose transport with the combination of AICAR plus contraction. These data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.

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Crossref · 10.2337/diabetes.47.8.1369

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Authors: Hayashi, T., Hirshman, M. F., Kurth, E. J., Winder, W. W., & Goodyear, L. J.
Affiliations: Brigham Young University (US)
Brigham and Women's Hospital (US)
Corresponding author: Goodyear, L. J.
ORCID: Hayashi, T.
Hirshman, M. F.
Goodyear, L. J.
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1998-08-01
Volume: 47
Issue: 8
Pages: 1369-1373
ISSN: 0012-1797 (ISSN-L)
DOI: 10.2337/diabetes.47.8.1369
OpenAlex: W2031532881
Cited by: 774
References: 0
Citations by year: 2026: 3 · 2025: 7 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 11 · 2020: 12 · 2019: 13 · 2018: 20 · 2017: 24 · 2016: 24 · 2015: 36 · 2014: 31 · 2013: 21 · 2012: 33
FWCI: 11.28
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-42238, R01AR041438, AR-41438)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Keywords: AMPK, skeletal muscle glucose transport, muscle contraction, AICAR, insulin signaling, phosphatidylinositol 3-kinase, wortmannin, epitrochlearis muscle, 3-O-methylglucose transport
MeSH terms: Wortmannin, Aminoimidazole Carboxamide, Androstadienes, Animals, Biological Transport, Drug Synergism, Glucose, Hypoglycemic Agents, Insulin, Insulin Antagonists, Male, Multienzyme Complexes, Muscle Contraction, Protein Kinases, Ribonucleotides, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Muscle, Skeletal, Rats, AMP-Activated Protein Kinases

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Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport

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