Scholarlink

Objective <p>To explore the molecular mechanism by which protein tyrosine phosphatase 1B (PTP1B) enzyme regulates insulin resistance (IR) in diabetes mellitus, and the regulation of isoquercitrin (IS) on PTP1B <i>in vitro</i> and <i>in vivo</i>.</p> Methods <p><i>In vitro</i>, PTP1B overexpression plasmid was constructed and transiently transfected into human hepatocellular liver carcinoma (HepG2) cells. A co-inducer was prepared by mixing a 0.125 mmol/L palmitic acid solution with a 1.0 × 10<sup>−7</sup> mol/L insulin solution to induce IR cell mode. Glucose oxidase assay, quantitative real-time-polymerase chain reaction (qRT-PCR), and Western blot were used to detect the effects of 40 µmol/L IS on glucose uptake and mRNA and protein expressions of related factors on the insulin receptor substrate (IRS)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal pathway in the PTP1B overexpressed IR cell model, respectively. <i>In vivo</i>, PTP1B overexpression adeno-associated virus (Aav-PTP1B) was constructed and injected into the tail vein of mice (200 µ L/piece). The metabolic indicators of mice were measured after 14-d intragastric administration of IS (40 mg/kg). The pancreas tissue was excised to observe the morphology via hematoxylin-eosin staining. Additionally, qRT-PCR and Western blot assays were performed on the liver tissue of mice to determine the expressions of related factors on the IRS/PI3K/AKT signal pathway of db/db and wild type mice after the intervention of IS on Aav-PTP1B.</p> Results <p>In both <i>in vivo</i> and <i>in vitro</i> experiments, IS significantly improved IR, reduced levels of blood glucose, total cholesterol, triglycerides, and other metabolic indicators in mice, effectively controlled body weight, and restored pancreatic cell morphology (<i>P</i>&lt;0.05 or <i>P</i>&lt;0.01). At the genomic level, IS improved the expressions of related factors in the IRS/PI3K/AKT signaling pathway by regulating the expression of PTP1B (<i>P</i>&lt;0.05 or <i>P</i>&lt;0.01), thereby maintaining the homeostasis of the pathway.</p> Conclusion <p>IS can improve IR by inhibiting the IRS/PI3K/AKT signaling pathway through PTP1B intervention.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Isoquercitrin Improves Insulin Resistance by Inhibiting PTP1B-Regulated IRS/PI3K/AKT Signaling Pathway

  • 期刊论文

  • 发表日期：

    2025年11月7日

查看全文
  • Si-yu Liu,
  • Lu-jing Yu,
  • Sheng-nan Zhang,
  • Jia-kui Yue,
  • Guo-jun Jiang,
  • Si-hua Lu,
  • Ying-jia Li,
  • Jun-yu Meng,
  • Gui-hong Huang

摘要

Objective

To explore the molecular mechanism by which protein tyrosine phosphatase 1B (PTP1B) enzyme regulates insulin resistance (IR) in diabetes mellitus, and the regulation of isoquercitrin (IS) on PTP1B in vitro and in vivo.

Methods

In vitro, PTP1B overexpression plasmid was constructed and transiently transfected into human hepatocellular liver carcinoma (HepG2) cells. A co-inducer was prepared by mixing a 0.125 mmol/L palmitic acid solution with a 1.0 × 10−7 mol/L insulin solution to induce IR cell mode. Glucose oxidase assay, quantitative real-time-polymerase chain reaction (qRT-PCR), and Western blot were used to detect the effects of 40 µmol/L IS on glucose uptake and mRNA and protein expressions of related factors on the insulin receptor substrate (IRS)/phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal pathway in the PTP1B overexpressed IR cell model, respectively. In vivo, PTP1B overexpression adeno-associated virus (Aav-PTP1B) was constructed and injected into the tail vein of mice (200 µ L/piece). The metabolic indicators of mice were measured after 14-d intragastric administration of IS (40 mg/kg). The pancreas tissue was excised to observe the morphology via hematoxylin-eosin staining. Additionally, qRT-PCR and Western blot assays were performed on the liver tissue of mice to determine the expressions of related factors on the IRS/PI3K/AKT signal pathway of db/db and wild type mice after the intervention of IS on Aav-PTP1B.

Results

In both in vivo and in vitro experiments, IS significantly improved IR, reduced levels of blood glucose, total cholesterol, triglycerides, and other metabolic indicators in mice, effectively controlled body weight, and restored pancreatic cell morphology (P<0.05 or P<0.01). At the genomic level, IS improved the expressions of related factors in the IRS/PI3K/AKT signaling pathway by regulating the expression of PTP1B (P<0.05 or P<0.01), thereby maintaining the homeostasis of the pathway.

Conclusion

IS can improve IR by inhibiting the IRS/PI3K/AKT signaling pathway through PTP1B intervention.