Berberine Improves Inflammatory Responses of Diabetes Mellitus in Zucker Diabetic Fatty Rats and Insulin-Resistant HepG2 Cells through the PPM1B Pathway

Autor: Yuan Xiao Yang, Yu Ting Bao, Zhe Ming Li, Ling Xuan, Shi Jie Dai, Lu Ning Lin, Li Ting Ji, Chang Yu Li, Yang Sheng Wu, Yi Tao Chen, Xiao Jie Zhou, Jian Shu Lou
Rok vydání: 2020
Předmět:
0301 basic medicine
Berberine
Anti-Inflammatory Agents
Pharmacology
chemistry.chemical_compound
0302 clinical medicine
Cyclic AMP
Insulin
Immunology and Allergy
Mice
Knockout
biology
Chemistry
NF-kappa B
Glucose analog
Hep G2 Cells
General Medicine
LRP1
Protein Phosphatase 2C
Liver
030220 oncology & carcinogenesis
Research Article
Signal Transduction
Article Subject
Cell Survival
Immunology
Diabetes Mellitus
Experimental
03 medical and health sciences
Insulin resistance
Downregulation and upregulation
medicine
Animals
Humans
Gene Silencing
Protein kinase B
PI3K/AKT/mTOR pathway
Gene Expression Profiling
Computational Biology
RC581-607
medicine.disease
Rats
Disease Models
Animal
Glucose
030104 developmental biology
biology.protein
Insulin Resistance
Immunologic diseases. Allergy
Energy Metabolism
Biomarkers
GLUT4
Zdroj: Journal of Immunology Research, Vol 2020 (2020)
Journal of Immunology Research
ISSN: 2314-7156
2314-8861
DOI: 10.1155/2020/2141508
Popis: Berberine (BBR), a natural compound extracted from a Chinese herb, has been shown to effectively attenuate insulin resistance (IR) and inflammation in the clinic. However, its ameliorative mechanism against IR is not well defined. This study is aimed at investigating the effect of BBR and protein phosphatase, Mg2+/Mn2+-dependent 1B (PPM1B) on IR. Biochemical measurements and liver histopathology were detected using the biochemical analyzer and HE staining in ZDF rats, respectively. Microarray analysis of liver tissues was performed, and differentially expressed gene (DEG) levels were examined by quantitative real-time PCR (qPCR) and Western blot. Additionally, the effect of BBR was also explored in HepG2-IR cells. The glucose oxidase method and the fluorescent glucose analog were used to detect glucose consumption and uptake, respectively. The PKA inhibitor H89, ELISA, qPCR, Western blot, and immunofluorescence staining were employed to estimate the expression levels of related signaling pathways. To evaluate the roles of PPM1B, HepG2-IR cells were stably infected with lentivirus targeting PPM1B. The administration of BBR drastically decreased the body weight, urine volume, blood glucose, blood urea nitrogen (BUN), CHOL, hepatic index levels, and pathologic changes and improved ALB levels in ZDF rats with PPM1B upregulation. Furthermore, BBR effectively improves glucose consumption, uptake, and inflammation in HepG2-IR cells. The knockdown of PPM1B expression aggravated the inflammatory response and glycometabolism disorder in HepG2-IR cells. Mechanistically, a reversal in the expression of cAMP, PKA, PPM1B, PPARγ, LRP1, GLUT4, NF-κB p65, JNK, pIKKβ Ser181, IKKβ, IRS-1 Ser307, IRS-1, IRS-2 Ser731, IRS-2, PI3K p85, and AKT Ser473 contributes to ameliorate IR in HepG2-IR cells with BBR treatment. Altogether, these results suggest that BBR might regulate IR progression through the regulation of the cAMP, PKA, PPM1B, PPARγ, LRP1, GLUT4, NF-κB p65, JNK, pIKKβ Ser181, IKKβ, IRS-1 Ser307, IRS-1, IRS-2 Ser731, IRS-2, PI3K p85, and AKT Ser473 expression in the liver.
Databáze: OpenAIRE
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