Redox compartmentalization drives functional heterogeneity of mature insulin secretory vesicles in pancreatic β-cells.

ABSTRACT: Pancreatic β-cell function requires precise regulation of insulin secretory vesicles (ISVs), yet the redox heterogeneity within mature ISVs remains poorly defined. Here, we implement a novel oxidation-sensing system using NPY-fused DsRed1-E5 (Timer) targeted to mature ISVs in INS-1E and human Endoc-βH5 β-cell models. Leveraging Timer's oxidative color transition from green (Low-oxidative) to yellow-red (High-oxidative), supported by independent measurements using the established redox sensor Grx1-roGFP2, we resolve distinct ISV subpopulations. Strikingly, Krebs-Ringer Bicarbonate HEPES (KRBH) Buffer treatment amplified ISV redox heterogeneity through increasing cytosolic oxidation. Factor screening identified glutamine deprivation as the principal driver of this diversification. Spatial an

SUBMITTER: Zhuang L 

PROVIDER: S-EPMC12433490 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature