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Abstract Title:

Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats.

Abstract Source:

Eur J Pharmacol. 2020 Apr 15 ;873:173004. Epub 2020 Feb 8. PMID: 32045603

Abstract Author(s):

Shyamaladevi Babu, Madhan Krishnan, Ponnulakshmi Rajagopal, Vijayalakshmi Periyasamy, Vishnupriya Veeraraghavan, Ramajayam Govindan, Selvaraj Jayaraman

Article Affiliation:

Shyamaladevi Babu

Abstract:

In our previous study, we have shown thatβ-sitosterol (SIT) enhances glycemic control by increasing the activation of insulin receptor (IR) and glucose transporter 4 (GLUT4) proteins in adipose tissue. However, the possible role of SIT on the regulation of post-receptor insulin signal transduction is not known. Hence, the study was aimedto assess the effects of SIT on IRS-1/Akt mediated insulin signaling molecules in high-fat diet and sucrose induced type-2 diabetic rats. An oral effective dose of SIT (20 mg/kg b.wt) was given for 30 days to high fat-fed type-2 diabetic rats to find out whether SIT regulates IRS-1/Akt pathway of insulin signaling. The results showed that SIT attenuated the insulin receptor substrate-1 serine phosphorylation (p-IRS-1) (P = 0.0003). However, it up-regulated the mRNA expression of IR (P = 0.0036) and post-receptor insulin signaling molecules such as IRS-1 (P < 0.0001), β-arrestin-2 (P < 0.0058), Akt (P = 0.0008), AS160 (P = 0.0030) and GLUT4 (P < 0.0001) with a concomitant increase in the levels of IRS-1(P < 0.0001), p-IRS1-1(P = 0.0014), Akt (P < 0.0001), p-Akt(P = 0.0006; P < 0.0001), AS160 and p-AS160(P < 0.0001) compared with type-2 diabetic rats. In Silico analysis was also performed and it showed that SIT possesses the greater binding affinity with β-arrestin-2, c-Src, and IRS-1 as well as Akt proteins and proved to attenuate insulin resistance as this study coincides with in vivo findings. Ourpresent study clearly shows that SIT attenuates high fat diet-induced detrimental changes in adipose tissue. Therefore, it is concluded from the present findings that, SIT could be used as potential therapeutic phytomedicine for the management of type-2 diabetes.

Study Type : Animal Study

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