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Selective Inhibition of PTP1B by Vitalboside A from Syzygium cumini Enhances Insulin Sensitivity and Attenuates Lipid Accumulation Via Partial Agonism to PPARγ: In Vitro and In Silico Investigation.

Authors :
Thiyagarajan G
Muthukumaran P
Sarath Kumar B
Muthusamy VS
Lakshmi BS
Source :
Chemical biology & drug design [Chem Biol Drug Des] 2016 Aug; Vol. 88 (2), pp. 302-12. Date of Electronic Publication: 2016 Apr 06.
Publication Year :
2016

Abstract

Although antidiabetic drugs show good insulin-sensitizing property for T2DM, they also exhibit undesirable side-effects. Partial peroxisome proliferator-activated receptor γ agonism with protein tyrosine phosphatase 1B inhibition is considered as an alternative therapeutic approach toward the development of a safe insulin sensitizer. Bioactivity-based fractionation and purification of Syzygium cumini seeds led to the isolation and identification of bifunctional Vitalboside A, which showed antidiabetic and anti-adipogenic activities, as measured by glucose uptake in L6 and 3T3-L1 adipocytes and Nile red assay. A non-competitive allosteric inhibition of protein tyrosine phosphatase 1B by Vitalboside A was observed, which was confirmed by docking studies. Inhibitor studies with wortmannin and genistein showed an IRTK- and PI3K-dependent glucose uptake. A PI3K/AKT-dependent activation of GLUT4 translocation and an inactivation of GSK3β were observed, confirming its insulin-sensitizing potential. Vitalboside A exhibited partial transactivation of peroxisome proliferator-activated receptor γ with an increase in adiponectin secretion, which was confirmed using docking analysis. Vitalboside A is a bifunctional molecule derived from edible plant showing inhibition of PTP1B and partial agonism to peroxisome proliferator-activated receptor γ which could be a promising therapeutic agent in the management of obesity and diabetes.<br /> (© 2016 John Wiley & Sons A/S.)

Details

Language :
English
ISSN :
1747-0285
Volume :
88
Issue :
2
Database :
MEDLINE
Journal :
Chemical biology & drug design
Publication Type :
Academic Journal
Accession number :
26989847
Full Text :
https://doi.org/10.1111/cbdd.12757