Quercetin, a Lead Compound against Type 2 Diabetes Ameliorates Glucose Uptake via AMPK Pathway in Skeletal Muscle Cell Line
Open accessAbstract
Herein we investigated the molecular mechanism of action of the citrus flavonoid, quercetin in skeletal muscle cells (L6 myotubes). Taking advantage of protein kinase inhibitors, we proved that the effect of quercetin on 2-NBDG uptake in L6 myotubes was not through insulin signaling pathway, but through adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK. An increase in the cellular AMP to ATP ratio on pretreatment may account for AMPK activation which was coupled with a transient change in mitochondrial membrane potential. In addition, quercetin triggered a rise in intracellular calcium suggesting that calcium-calmodulin mediated protein kinase (CaMKK) may also be involved. Quercetin shared a similar mechanism with the well-known drug metformin, highlighting it as a promising compound for the management of type 2 diabetes. The AMPK signaling pathway could contribute to correction of insulin resistance through bypassing the insulin-regulated system for GLUT4 translocation.
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Quercetin can increase glucose uptake through GLUT4 transporter.
“Moreover, it can increase glucose uptake through GLUT4 transporter [33].”
From Mediterranean Diet as an Antioxidant: The Impact on Metabolic Health and Overall Wellbeing (2021) · cites this paper as [33]
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“Also, quercetin can enhance the uptake of glucose in skeletal myocytes through an AMPK-dependent up-regulation of glucose transporter GLUT-4, which may occur independently of the insulin signaling under oxidative stress conditions [60].”
BackgroundScannell, N., Villani, A., Moran, L., & Mantzioris, E. (2025) · Proceedings of the Nutrition Society · doi:10.1017/s0029665124007584 · Cited by 12 · see citing works
“…possess anti-diabetic properties including enhancing the function of glucose transporters, reducing metabolic stress in mitochondria, improved beta cell functioning and attenuation of oxidative stress in response to inflammation in tissues including muscle, liver and adipose (160 – 162) .”
- Authors
- Dhanya, R., Arya, A. D., Nisha, P., & Jayamurthy, P.
- Affiliations
- National Institute for Interdisciplinary Science and Technology (IN)
- Corresponding author
- Jayamurthy, P.
- Venue
- Frontiers in Pharmacology
- Publisher
- Frontiers Media SA
- Published
- 2017-06-08
- Volume
- 8
- Pages
- 336-336
- ISSN
- 1663-9812 (ISSN-L)
- PMC
- PMC5462925
- OpenAlex
- W2617658608
- Cited by
- 167
- References
- 40
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 25 · 2023: 17 · 2022: 23 · 2021: 21 · 2020: 12 · 2019: 17 · 2018: 11 · 2017: 1 · 2012: 1
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Pharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Kerala State Council for Science, Technology and Environment
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Keywords
- quercetin, type 2 diabetes, glucose uptake, AMPK signaling, p38 MAPK, CaMKK, L6 myotubes, skeletal muscle, insulin resistance, GLUT4 translocation, metformin, citrus flavonoids, mitochondrial membrane potential, intracellular calcium
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