SERCA2 regulates proinsulin processing and processing enzyme maturation in pancreatic beta cells.

ABSTRACT:

Aims/hypothesis

Increased circulating levels of incompletely processed insulin (i.e. proinsulin) are observed clinically in type 1 and type 2 diabetes. Previous studies have suggested that Ca²⁺ signalling within beta cells regulates insulin processing and secretion; however, the mechanisms that link impaired Ca²⁺ signalling with defective insulin maturation remain incompletely understood.

Methods

We generated mice with beta cell-specific sarcoendoplasmic reticulum Ca²⁺ ATPase-2 (SERCA2) deletion (βS2KO mice) and used an INS-1 cell line model of SERCA2 deficiency. Whole-body metabolic phenotyping, Ca²⁺ imaging, RNA-seq and protein processing assays were used to determine how loss of SERCA2 impacts beta cell function. To test key fin

SUBMITTER: Iida H 

PROVIDER: S-EPMC10542743 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature