Astragaloside IV Regulates Insulin Resistance and Inflammatory Response of Adipocytes via Modulating CTRP3 and PI3K/AKT Signaling

• Published in: Diabetes therapy Vol. 13; no. 11-12; pp. 1823 - 1834
• Main Authors: Zhang, Yue, Xu, Guangning, Huang, Baoyi, Chen, Dongni, Ye, Renqun
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.12.2022; Springer; Springer Nature B.V
• Subjects: Adipocytes; Astragalus (Plants); Cardiology; Care and treatment; Chemical properties; Cytokines; Diabetes; Endocrinology; Fat cells; Glucose; Health aspects; Insulin; Insulin resistance; Internal Medicine; Kinases; Medicine; Medicine & Public Health; Original Research; Physiological aspects; Protein kinases; Saponins; Tumor necrosis factor-TNF; China; T2DM; Inflammation; CTRP3; Astragaloside IV; Glucose consumption; PI3K/Akt
• ISSN: 1869-6953; 1869-6961
• DOI: 10.1007/s13300-022-01312-1

Introduction Emerging evidence showed that adipocytes are important regulators in controlling insulin resistance in type 2 diabetes mellitus (T2DM). So far, compounds isolated from natural plants have been widely studied for their roles in alleviating T2DM-associated complications. This work evaluated the actions of astragaloside IV (AS-IV) on insulin resistance and inflammatory biomarker expression in adipocytes and explored the potential mechanisms. Methods Glucose consumption of the adipocytes was determined by a glucose assay kit; the mRNA expression levels of glucose transporter type 4 (GLUT-4), interleukin-6 (IL-6), TNF-α and C1q tumor necrosis factor-related protein 3 (CTRP3) were measured by quantitative real-time PCR (qRT-PCR); the protein levels were determined by western blot assay and enzyme-linked immunosorbent assay. Results AS-IV concentration-dependently increased glucose consumption in the insulin resistance adipocytes. Further qRT-PCR results showed that AS-IV concentration-dependently reduced adipocyte IL-6 and TNF-α expression. Moreover, GLUT-4 expression in adipocytes was also significantly upregulated by AS-IV. Furthermore, we found that AS-IV concentration-dependently increased CTRP3 expression in adipocytes. CTRP3 silence decreased glucose consumption, upregulated IL-6 and TNF-α expression and downregulated GLUT-4 mRNA expression in 200 µM AS-IV-treated adipocytes. Moreover, AS-IV treatment enhanced the activity of phosphoinositide 3-kinase (PI3K)/AKT signaling in adipocytes, which was markedly attenuated by CTRP3 silencing. Importantly, inhibition of PI3K/AKT signaling also attenuated AS-IV induced an increase in glucose consumption and GLUT-4 expression and a decrease in IL-6 and TNF-α expression of adipocytes. Conclusions Collectively, our data indicated that AS-IV attenuated insulin resistance and inflammation in adipocytes via targeting CTRP3/PI3K/Akt signaling.