The DOI matches its Crossref record; 53 of the 55 references it cites were found in a registry or an index.
Stimulation of AMP-activated protein kinase and enhancement of basal glucose uptake in muscle cells by quercetin and quercetin glycosides, active principles of the antidiabetic medicinal plant Vaccinium vitis-idaea
Abstract
Several medicinal plants that stimulate glucose uptake in skeletal muscle cells were identified from among species used by the Cree of Eeyou Istchee of northern Quebec to treat symptoms of diabetes. This study aimed to elucidate the mechanism of action of one of these products, the berries of Vaccinium vitis idaea, as well as to isolate and identify its active constituents using a classical bioassay-guided fractionation approach. Western immunoblot analysis in C2C12 muscle cells revealed that the ethanol extract of the berries stimulated the insulin-independent AMP-activated protein kinase (AMPK) pathway. The extract mildly inhibited ADP-stimulated oxygen consumption in isolated mitochondria, an effect consistent with metabolic stress and the ensuing stimulation of AMPK. This mechanism is highly analogous to that of Metformin. Fractionation guided by glucose uptake activity resulted in the isolation of ten compounds. The two most active, quercetin-3-O-glycosides, enhanced glucose uptake by 38-59% (50 muM; 18 h treatment) in the absence of insulin. Quercetin aglycone, a minor constituent, stimulated uptake by 37%. The quercetin glycosides and the aglycone stimulated the AMPK pathway at concentrations of 25-100 muM, but only the aglycone inhibited ATP synthase in isolated mitochondria (by 34 and 79% at 25 and 100 muM, respectively). This discrepancy suggests that the activity of the glycosides may require hydrolysis to the aglycone form. These findings indicate that quercetin and quercetin 3-O-glycosides are responsible for the antidiabetic activity of V. vitis crude berry extract mediated by AMPK. These common plant products may thus have potential applications for the prevention and treatment of insulin resistance and other metabolic diseases.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“Additionally, the dose-response analysis suggested a 5% reduction of T2D risk for each 300 mg/day increment of total flavonoids intake [59].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [59]
In the citing paper
“Quercetin has been reported to modulate fatty acid metabolism in vitro with an increase in fatty acid β-oxidation being reported in C2C12 myotubes, hepatocytes and Hela cells (Suchankova et al., 2009; Eid et al., 2010).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Eid et al., 2010
Citations
Cites
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
The Flavonoids: Advances in Research.
Richardson, P. M., Harborne, J. B., & Mabry, T. J. (1984) · Brittonia · doi:10.2307/2806301 · Cited by 1,429
Lee, Y. S., Kim, W. S., Kim, K. H., Yoon, M. J., Cho, H. J., Shen, Y., Ye, J.-M., Lee, C. H., Oh, W. K., Kim, C. T., et al. (2006) · Diabetes · doi:10.2337/db06-0006 · Cited by 1,054
Zang, M., Xu, S., Maitland, K. A., Zuccollo, A., Hou, X., Jiang, B., Wierzbicki, M., Verbeuren, T. J., & Cohen, R. A. (2006) · Diabetes · doi:10.2337/db05-1188 · Cited by 672
Antidiabetic effects of quercetin in streptozocin-induced diabetic rats
Vessal, M., Hemmati, M., & Vasei, M. (2003) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/s1532-0456(03)00140-6 · Cited by 625
Viollet, B., Foretz, M., Guigas, B., Horman, S., Dentin, R., Bertrand, L., Hue, L., & Andréelli, F. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.108506 · Cited by 543
The anti-obesity effect of quercetin is mediated by the AMPK and MAPK signaling pathways
Ahn, J., Lee, H., Kim, S., Park, J., & Ha, T. Y. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.06.077 · Cited by 524
Quercetin: potentials in the prevention and therapy of disease
Bischoff, S. C. (2008) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32831394b8 · Cited by 487
Hwang, J.-T., Park, I.-J., Shin, J.-I., Lee, Y. K., Lee, S., Baik, H. W., Ha, J., & Park, O. J. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.09.195 · Cited by 484
Hayashi, T., Hirshman, M. F., Fujii, N., Habinowski, S. A., Witters, L. A., & Goodyear, L. J. (2000) · Diabetes · doi:10.2337/diabetes.49.4.527 · Cited by 447
Research works printed but not linked: 3
- Spoor, 2007, Mechanisms of anti-diabetic activity of extracts of selected medicinal plant species of the Canadian boreal forest, Diabetes Vasc. Dis. Res., 4, 156
- Johnson, 1967, Methods in Enzymology
- Cavaliere, 2007, Glucophage: diabetic drug based on traditional herb celebrates 50 years of use, HerbalGram, 76, 44
Cited by
Sorted by citations
AL-Ishaq, R. K., Abotaleb, M., Kubatka, P., Kajo, K., & Büsselberg, D. (2019) · Biomolecules · doi:10.3390/biom9090430 · Cited by 816
Recent advances in understanding the anti-diabetic actions of dietary flavonoids
Babu, P. V. A., Liu, D., & Gilbert, E. R. (2013) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2013.06.003 · Cited by 558
Mitochondrial dysfunction and insulin resistance: an update
Montgomery, M. K., & Turner, N. A. (2014) · Endocrine Connections · doi:10.1530/ec-14-0092 · Cited by 549
Molecular Mechanisms of the Anti-Obesity and Anti-Diabetic Properties of Flavonoids
Kawser Hossain, M., Abdal Dayem, A., Han, J., Yin, Y., Kim, K., Kumar Saha, S., Yang, G.-M., Choi, H., & Cho, S.-G. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17040569 · Cited by 495
Flavonols and cardiovascular disease
Perez-Vizcaino, F., & Duarte, J. (2010) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2010.09.002 · Cited by 393
Metadata
- Authors
- Eid, H. M., Martineau, L. C., Saleem, A., Muhammad, A., Vallerand, D., Benhaddou-Andaloussi, A., Nistor, L., Afshar, A., Arnason, J. T., & Haddad, P. S.
- Affiliations
- Canadian Institutes of Health Research (CA)
- University of Ottawa (CA)
- Corresponding author
- Haddad, Pierre S.
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2010-01-19
- Volume
- 54
- Issue
- 7
- Pages
- 991-1003
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- OpenAlex
- W2157304833
- Cited by
- 218
- References
- 55
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 17 · 2023: 16 · 2022: 22 · 2021: 16 · 2020: 13 · 2019: 11 · 2018: 19 · 2017: 7 · 2016: 13 · 2015: 16 · 2014: 18 · 2013: 8 · 2012: 14
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
- Keywords
- AMPK, quercetin, quercetin glycosides, quercetin aglycone, lingonberry, glucose uptake, skeletal muscle, insulin-independent glucose uptake, antidiabetic activity, bioassay-guided fractionation, ATP synthase inhibition, mitochondrial oxygen consumption, metabolic stress, insulin resistance
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Line, Diabetes Mellitus, Fruit, Glucose, Glycosides, Hydrogen-Ion Concentration, Hypoglycemic Agents, Kinetics, Male, Mitochondria, Liver, Osmolar Concentration, Plant Extracts, Plants, Medicinal, Quebec, Quercetin, Rats, Wistar, Hepatocytes, Mitochondrial Proton-Translocating ATPases, Vaccinium vitis-idaea, Myoblasts, Skeletal, Mice, Rats, AMP-Activated Protein Kinases
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
