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

Area of Science:

• Molecular Biology
• Biochemistry
• Endocrinology

Background:

• Insulin resistance (IR) is a hallmark of diabetes mellitus, characterized by impaired insulin signaling.
• Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin signaling and a therapeutic target for IR.
• Isoquercitrin (IS), a flavonoid, has shown potential in metabolic disease management.

Purpose of the Study:

• To investigate the molecular mechanism of PTP1B in regulating IR.
• To determine the effect of isoquercitrin (IS) on PTP1B activity and insulin signaling in vitro and in vivo.

Main Methods:

• In vitro: PTP1B overexpression in HepG2 cells, induction of IR model, and assessment of glucose uptake and signaling pathway components (IRS/PI3K/AKT) using qRT-PCR and Western blot following IS treatment.
• In vivo: Tail vein injection of Aav-PTP1B in mice, followed by IS administration. Metabolic indicators, pancreatic morphology, and liver signaling pathway expressions were analyzed.
• Quantitative real-time-polymerase chain reaction (qRT-PCR) and Western blot were employed to assess gene and protein expression levels.

Main Results:

• IS significantly ameliorated IR, reduced blood glucose, cholesterol, and triglyceride levels, controlled body weight, and restored pancreatic morphology in both in vitro and in vivo models.
• IS regulated PTP1B expression, thereby modulating the IRS/PI3K/AKT signaling pathway.
• IS treatment led to significant improvements in metabolic indicators and pathway homeostasis (P<0.05 or P<0.01).

Conclusions:

• Isoquercitrin (IS) demonstrates significant potential in improving insulin resistance (IR).
• IS acts by inhibiting the IRS/PI3K/AKT signaling pathway via PTP1B intervention.
• The findings support IS as a therapeutic agent for managing diabetes mellitus and associated metabolic dysfunctions.