SORLA mediates endocytic uptake of proIAPP and protects against islet amyloid deposition.

ABSTRACT:

Objective

Sorting-related receptor with type A repeats (SORLA) is a neuronal sorting receptor that prevents accumulation of amyloid-beta peptides, the main constituent of senile plaques in Alzheimer disease. Recent transcriptomic studies show that SORLA transcripts are also found in beta cells of pancreatic islets, yet the role of SORLA in islets is unknown. Based on its protective role in reducing the amyloid burden in the brain, we hypothesized that SORLA has a similar function in the pancreas via regulation of amyloid formation from islet amyloid polypeptide (IAPP).

Methods

We generated human IAPP transgenic mice lacking SORLA (hIAPP:SORLA KO) to assess the consequences of receptor deficiency for islet histopathology and function in vivo. Using both primary islet cells an

SUBMITTER: Shih AZL 

PROVIDER: S-EPMC9474563 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature