NLRP3 inflammasome activation and disruption of IRS-1/PI3K/AKT signaling: Potential mechanisms of arsenic-induced pancreatic beta cells dysfunction in rats
Yonglian Liu, Wenjuan Wang, Bing Liang, Zhonglan Zou, Aihua Zhang
Abstract
-treated INS-1 cells exhibited a dose-dependent reduction in glucose-stimulated insulin secretion. Furthermore, arsenic exposure in these cells activated the NLRP3 inflammasome, suppressed the IRS-1/PI3K/AKT signaling pathway, and downregulated insulin secretion regulatory molecules (PDX-1, GLUT2, and GCK). Notably, these arsenic-induced effects were reversed by MCC950, an NLRP3 inflammasome inhibitor, and Extendin-4, an agonist of the IRS-1/PI3K/AKT signaling pathway. Collectively, these findings demonstrate that NLRP3 inflammasome activation disrupts the IRS-1/PI3K/AKT signaling pathway, contributing to arsenic-induced pancreatic beta cells dysfunction in rats.
Topics & Concepts
PI3K/AKT/mTOR pathwayInflammasomeProtein kinase BArsenicCell biologyChemistrySignal transductionCancer researchBETA (programming language)BiologyBiochemistryReceptorComputer scienceOrganic chemistryProgramming languagePancreatitis Pathology and TreatmentInflammasome and immune disordersBiomedical Research and Pathophysiology