Objective:

2

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:

2

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 μL/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 stai

ning. 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:

2

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:

2

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