Autophagy is a major regulator of beta cell insulin homeostasis.

ABSTRACT:

Aims/hypothesis

We studied the role of protein degradation pathways in the regulation of insulin production and secretion and hypothesised that autophagy regulates proinsulin degradation, thereby modulating beta cell function.

Methods

Proinsulin localisation in autophagosomes was demonstrated by confocal and electron microscopy. Autophagy was inhibited by knockdown of autophagy-related (ATG) proteins and using the H(+)-ATPase inhibitor bafilomycin-A1. Proinsulin and insulin content and secretion were assessed in static incubations by ELISA and RIA.

Results

Confocal and electron microscopy showed proinsulin localised in autophagosomes and lysosomes. Beta-Atg7 (-/-) mice had proinsulin-containing sequestosome 1 (p62 [also known as SQSTM1])(+) aggregates in beta cells, i

SUBMITTER: Riahi Y 

PROVIDER: S-EPMC5912938 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature