Pancreastatin inhibitor PSTi8 attenuates hyperinsulinemia induced obesity and inflammation mediated insulin resistance via MAPK/NOX3-JNK pathway.

Pancreastatin inhibitor PSTi8 attenuates hyperinsulinemia induced obesity and inflammation mediated insulin resistance via MAPK/NOX3-JNK pathway. Eur J Pharmacol. 2019 Oct 03;:172723 Authors: Gupta AP, Syed AA, Garg R, Goand UK, Singh P, Riyazuddin M, Valicherla GR, Husain A, Gayen JR Abstract Pancreastatin (PST), a chromograninA derived peptide has anti-insulin effects and plays a significant role in obesity-induced insulin resistance. In obesity and type 2 diabetes mellitus, both insulin and PST level are elevated, but it is not clearly understood how anti-insulin effect of PST get regulated in hyperinsulinemic state. Simultaneously we have explored pancreastatin inhibitor PSTi8 against the native PST in the same hyperinsulinemic state. In in-vitro studies, we found that PST treatment increases lipid droplets and reactive oxygen species production in 3T3L1 adipocyte cells and theses effects of PST was found synergistic with chronic-insulin treatment. Treatment of PSTi8 in 3T3L1 adipocytes attenuates PST effect on lipid droplet formation and reactive oxygen species production. We further validated these findings in epididymal white adipose tissue of C57BL/6 mice, implanted with mini-osmotic insulin pump with and without PSTi8 for 4 weeks. We found that chronic hyperinsulinemia enhanced PST levels in circulation which in turn induces expression of various pro-inflammatory cytokines and oxidative stress. In addition, it also stimulate...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research