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

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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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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: Vallerand, Diane
Arnason, John T.
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
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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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

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