IRE1-XBP1 pathway regulates oxidative proinsulin folding in pancreatic β cells.

ABSTRACT: In mammalian pancreatic β cells, the IRE1α-XBP1 pathway is constitutively and highly activated under physiological conditions. To elucidate the precise role of this pathway, we constructed β cell-specific Ire1α conditional knockout (CKO) mice and established insulinoma cell lines in which Ire1α was deleted using the Cre-loxP system. Ire1α CKO mice showed the typical diabetic phenotype including impaired glycemic control and defects in insulin biosynthesis postnatally at 4-20 weeks. Ire1α deletion in pancreatic β cells in mice and insulinoma cells resulted in decreased insulin secretion, decreased insulin and proinsulin contents in cells, and decreased oxidative folding of proinsulin along with decreased expression of five protein disulfide isomerases (PDIs): PDI

SUBMITTER: Tsuchiya Y 

PROVIDER: S-EPMC5881499 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature