The DOI matches its Crossref record.
Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism.
Open accessAbstract
5'AMP-activated protein kinase (AMPK) can be activated in response to cellular fuel depletion and leads to switching off ATP-consuming pathways and switching on ATP-regenerating pathways in many cell types. We have hypothesized that AMPK is a central mediator of insulin-independent glucose transport, which enables fuel-depleted muscle cells to take up glucose for ATP regeneration under conditions of metabolic stress. To test this hypothesis, rat epitrochlearis muscles were isolated and incubated in vitro under several conditions that evoke metabolic stress accompanied by intracellular fuel depletion. Rates of glucose transport in the isolated muscles were increased by all of these conditions, including contraction (5-fold above basal), hypoxia (8-fold), 2,4-dinotrophenol (11-fold), rotenone (7-fold), and hyperosmolarity (8-fold). All of these stimuli simultaneously increased both alpha1 and alpha2 isoform-specific AMPK activity. There was close correlation between alpha1 (r2 = 0.72) and alpha2 (r2 = 0.67) AMPK activities and the rate of glucose transport, irrespective of the metabolic stress used, all of which compromised muscle fuel status as judged by ATP, phosphocreatine, and glycogen content. 5-Aminoimidazole-4-carboxamide ribonucleoside, a pharmacological AMPK activator that is metabolized to an AMP-mimetic ZMP, also increased both glucose transport and AMPK activity but did not change fuel status. Insulin stimulated glucose transport by 6.5-fold above basal but did not affect AMPK activity. These results suggest that the activation of AMPK may be a common mechanism leading to insulin-independent glucose transport in skeletal muscle under conditions of metabolic stress.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Exercise training is a well-known AMPK activator in the skeletal muscle of rodents and humans26-28.”
From Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence (2024) · cites this paper as [26]
In the citing paper
“Both AMPK α1 and α2 are activated during exercise; however, α1 activity appears to be increased during high intensity muscle contractions, which are equivalent to >100% maximal oxygen consumption (VO2 Max; measure of maximal exercise capacity) [59,62,63].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [63]
In the citing paper
“Both AMPK α1 and α2 are activated during exercise; however, α1 activity appears to be increased during high intensity muscle contractions, which are equivalent to >100% maximal oxygen consumption (VO2 Max; measure of maximal exercise capacity) [59,62,63].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [63]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Still being checked.
Cited by
Sorted by citations
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652
Self-citationYamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems
Tacar, O., Sriamornsak, P., & Dass, C. R. (2012) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.2012.01567.x · Cited by 2,528
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053
Metadata
- Authors
- Hayashi, T., Hirshman, M. F., Fujii, N., Habinowski, S. A., Witters, L. A., & Goodyear, L. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2000-04-01
- Volume
- 49
- Issue
- 4
- Pages
- 527-531
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2106324494
- Cited by
- 447
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 10 · 2017: 19 · 2016: 20 · 2015: 23 · 2014: 12 · 2013: 23 · 2012: 24
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Joslin Diabetes Center
- Manpei Suzuki Diabetes Foundation
- Japan Society for the Promotion of Science
- National Institute of Diabetes and Digestive and Kidney Diseases (DK375712)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR45670, AR-42238, R01AR045670)
- 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 › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- AMPK, insulin-independent glucose transport, metabolic stress, skeletal muscle, fuel depletion, ATP regeneration, hypoxia, rotenone, 2,4-dinitrophenol, hyperosmolarity, AMPK isoforms
- MeSH terms
- Adenosine Monophosphate, Adenosine Triphosphate, Animals, Biological Transport, Creatine, Enzyme Activation, Glucose, Kinetics, Male, Muscle Contraction, Osmolar Concentration, Phosphocreatine, Protein Kinases, Rotenone, Stress, Physiological, Uncoupling Agents, Rats, Sprague-Dawley, Muscle, Skeletal, 2,4-Dinitrophenol, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
