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Research Article | Open Access

Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism

William T. Moorea,b, Jing Luoa, Dongmin Liua,c( )
Department of Human Nutrition, Foods and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg 24060, USA
Department of Biology and Chemistry, Liberty University, Lynchburg 24515, USA
Department of Human Nutrition, Foods and Exercise, Virginia Tech, 1981 Kraft Drive, Corporate Research Center, Blacksburg 24061, USA

Peer review under responsibility of KeAi Communications Co., Ltd.

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Abstract

Insulin resistance is a hallmark of type-2 diabetes (T2D) pathogenesis. Because skeletal muscle (SkM) is the major tissue for insulin-mediated glucose disposal, insulin resistance in SkM is considered a major risk factor for developing T2D. Thus, the identification of compounds that enhance the ability of SkM to take up glucose is a promising strategy for preventing T2D. Our previous work showed that kaempferol, a flavonol present in many foods, improves insulin sensitivity in obese mice, however, the mechanism underlying this beneficial action remains unclear. Here, we show that kaempferol directly stimulates glucose uptake and prevents lipotoxicity-impaired glucose uptake in primary human SkM. Kaempferol stimulates Akt phosphorylation in a time-dependent manner in human SkM cells. The effect of kaempferol on glucose uptake was blunted by inhibition of glucose transporter 4, phosphoinositide 3-kinase (PI3K), or AMPK. In addition, kaempferol induced AMPK phosphorylation, and inhibition of AMPK prevented kaempferol-stimulated Akt phosphorylation. In vivo, kaempferol administration induced rapid glucose disposal accompanied with increased Akt and AMPK phosphorylation in SkM tissue of the mice. Taken together, these findings suggest that kaempferol stimulates glucose uptake in SkM via an AMPK/Akt dependent mechanism, and it may be a viable therapeutic agent for insulin resistance.

Keywords

Insulin resistanceSkeletal muscleAMPKAktKaempferol

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Food Science and Human Wellness
Volume 12 Issue 6,
November 2023
Pages 2087-2094
DOI: 10.1016/j.fshw.2023.03.028
Cite this article:
Moore WT, Luo J, Liu D. Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism. Food Science and Human Wellness, 2023, 12(6): 2087-2094. https://doi.org/10.1016/j.fshw.2023.03.028

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Received: 22 February 2022
Revised: 10 March 2022
Accepted: 23 March 2022
Published: 04 April 2023
© 2023 Beijing Academy of Food Sciences.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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