Hesperetin-copper (II) complex improves liver glucose metabolism by regulating the IRS-1/PI3K/AKT signaling pathway in T2DM mice


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Hesperetin-copper (II) complex improves liver glucose metabolism by regulating the IRS-1/PI3K/AKT signaling pathway in T2DM mice

The metal complexes of flavonoids have attracted widespread attention because of their distinct structural and functional characteristics. Hesperetin-Cu(II) complex [Hsp-Cu(II)] showed good hypoglycemic potential, but its hypoglycemic effect and mechanism in vivo are still vague. This study aimed to investigate the hypoglycemic effect of Hsp-Cu(II) on type 2 diabetic (T2DM) mice and its underlying mechanism. The results showed that Hsp-Cu(II) (50 mg/kg) effectively improved hyperglycemia and dyslipidemia, increased the fast insulin level and HOMA-IR to alleviate the insulin resistance in the T2DM mice. Compared with the Diseased group, treatment of Hsp-Cu(II) at 50 mg/kg reduced the activities of α-amylase, phosphoenolpyruvate carboxy kinase (PEPCK) and glucose 6-phosphatase (G6Pase) by 31.7%, 45.5% and 35.1%, respectively; elevated the level of glutathione and activities of superoxide dismutase and catalase by 27.2%, 71.7% and 36.7%, respectively, and decreased the malondia ldehyde content by 23.6% to improve the liver antioxidant abilities; reduced the activities of alanine aminotransferase and aspartate aminotransferase by 15.6% and 28.1%, as well as the levels of inflammatory factors to relieve liver damage. In addition, Hsp-Cu(II) activated the insulin receptor substrate-1/phosphoinositide-3-kinase/protein kinase B (IRS-1/PI3K/AKT) signaling pathway to up-regulate the protein expression levels of phospho-glycogen synthase kinase-3β (p-GSK-3β) and phospho-fork head box transcription factor O1 (p-FoxO1) and down-regulate the mRNA expression of PEPCK and G6Pase. Therefore, Hsp-Cu(II) may regulate hepatic glucose metabolism through IRS-1/PI3K/AKT‒GSK3β pathways to increase the hepatic glycogen content and IRS-1/PI3K/AKT‒FoxO1‒PEPCK/G6Pase pathways to inhibit gluconeogenesis, maintain hepatic glucose homeostasis, thus exerting the hypoglycemia effect in T2DM. These discoveries may provide a scientific basis for developing Hsp-Cu(II) as a food f unction factor to alleviate T2DM. © 2024 Elsevier Ltd

Authors : Peng X.; Wei Y.; Gong D.; Zhang G.

Source : Elsevier Ltd

Article Information

Year 2024
Type Article
DOI 10.1016/j.fbio.2024.105408
ISSN 22124292
Volume 62

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