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Cited by 218Natural Antidiabetic Agents StudiesMetabolism, Diabetes, and CancerPhytochemistry and Biological Activities

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

Eid, Hoda M., Martineau, Louis C., Saleem, Ammar, Muhammad, Asim, Vallerand, Diane, Benhaddou-Andaloussi, Ali, Nistor, Lidia, Afshar, Arvind, Arnason, John T., Haddad, Pierre S.·2010·Molecular Nutrition & Food Research
DOI 10.1002/mnfr.200900218
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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.

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Research works printed but not linked: 3

  1. 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
  2. Johnson, 1967, Methods in Enzymology
  3. Cavaliere, 2007, Glucophage: diabetic drug based on traditional herb celebrates 50 years of use, HerbalGram, 76, 44

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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.
ORCID
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
DOI
10.1002/mnfr.200900218
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
Licence
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 2051 d)
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

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