5‑Aminolevulinic acid combined with ferrous iron improves glucose tolerance in high‑fat diet‑fed mice via upregulation of glucose transporter 1

Kuroda,Yasushi; Kamiya,Atsuko; Ishii,Takuya; Ishizuka,Masahiro; Yamashita,Yoko; Ashida,Hitoshi

doi:10.3892/etm.2021.10889

5‑Aminolevulinic acid combined with ferrous iron improves glucose tolerance in high‑fat diet‑fed mice via upregulation of glucose transporter 1

Authors:
- Yasushi Kuroda
- Atsuko Kamiya
- Takuya Ishii
- Masahiro Ishizuka
- Yoko Yamashita
- Hitoshi Ashida
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Affiliations: SBI Pharmaceuticals Co., Ltd., Tokyo 106‑6020, Japan, Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657‑8501, Japan
Published online on: October 15, 2021 https://doi.org/10.3892/etm.2021.10889
Article Number: 1454

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Abstract

Decreased mitochondrial metabolism suppresses glucose metabolism, resulting in obesity and diabetes. The present study aimed to investigate mechanisms underlying the 5‑aminolevulinic acid (5‑ALA) hydrochloride‑mediated increase in glucose uptake in high‑fat diet (HFD)‑fed mice in vivo and C2C12 myotube cells in vitro. C57BL/6N male mice (20 weeks old) were fed either HFD or normal diet (ND) for 4 weeks. A total of five HFD‑fed mice were orally administered with 300 mg/kg 5‑ALA hydrochloride and 47.1 mg/kg sodium ferrous citrate (SFC; HFD + 5‑ALA/SFC), whereas ND and other HFD‑fed mice were orally administered with saline. After 4 weeks, these mice were intraperitoneally administered with 2 g/kg glucose and 3.2 mg/kg 2‑deoxyglucose (2DG) for intraperitoneal glucose tolerance test (IPGTT) and glucose uptake test. Body weights, plasma glucose levels and the area under the curve of IPGTT were lower in mice treated with HFD + 5‑ALA/SFC compared with in those treated with HFD alone. 2DG uptake in the gastrocnemius muscle and heart were more significantly improved in the HFD + 5‑ALA/SFC mice compared with the HFD‑fed mice. Furthermore, 5‑ALA/SFC increased 2DG uptake in C2C12 cells to a similar level to the insulin‑treated group. Moreover, it increased glucose transport (GLUT)1 translocation in the plasma membrane by 2.5-fold relative to the controls without affecting GLUT1 expression; however, it had no effect on GLUT4 translocation. Therefore, 5‑ALA/SFC enhanced gastrocnemius and cardiac glucose uptake in HFD‑fed mice, and upregulated GLUT1 translocation to the plasma membrane, but not GLUT4 in C2C12 myotube cells. Therefore, it could potentially be used as a novel drug for the treatment of diabetes.

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