Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism
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 abil...
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| Format: | Article |
| Language: | English |
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Tsinghua University Press
2023-11-01
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| Series: | Food Science and Human Wellness |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453023000800 |
| _version_ | 1826819947043487744 |
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| author | William T. Moore Jing Luo Dongmin Liu |
| author_facet | William T. Moore Jing Luo Dongmin Liu |
| author_sort | William T. Moore |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T03:16:18Z |
| format | Article |
| id | doaj.art-a3b4a1b6c503405e833b41524c83c538 |
| institution | Directory Open Access Journal |
| issn | 2213-4530 |
| language | English |
| last_indexed | 2025-02-16T06:20:15Z |
| publishDate | 2023-11-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj.art-a3b4a1b6c503405e833b41524c83c5382025-02-03T06:54:16ZengTsinghua University PressFood Science and Human Wellness2213-45302023-11-0112620872094Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanismWilliam T. Moore0Jing Luo1Dongmin Liu2Department 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, USADepartment of Human Nutrition, Foods and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg 24060, USADepartment of Human Nutrition, Foods and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg 24060, USA; Department of Human Nutrition, Foods and Exercise, Virginia Tech, 1981 Kraft Drive, Corporate Research Center, Blacksburg 24061, USA; Corresponding author at: Department of Human Nutrition, Foods and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, 24060, USA.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.http://www.sciencedirect.com/science/article/pii/S2213453023000800KaempferolSkeletal muscleAMPKAktInsulin resistance |
| spellingShingle | William T. Moore Jing Luo Dongmin Liu Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism Food Science and Human Wellness Kaempferol Skeletal muscle AMPK Akt Insulin resistance |
| title | Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism |
| title_full | Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism |
| title_fullStr | Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism |
| title_full_unstemmed | Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism |
| title_short | Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism |
| title_sort | kaempferol improves glucose uptake in skeletal muscle via an ampk dependent mechanism |
| topic | Kaempferol Skeletal muscle AMPK Akt Insulin resistance |
| url | http://www.sciencedirect.com/science/article/pii/S2213453023000800 |
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