Modeling diabetic alpha cell dysfunction using stem cell-derived alpha cells.

ABSTRACT: Dysfunction of pancreatic alpha cells contributes to the pathophysiology of diabetes. Features of diabetic alpha cell dysfunction include glucagon hypersecretion, defects in proglucagon processing, and altered transcriptomic profile. The lack of an in vitro human alpha cell model has prevented the investigation, and potential correction, of these dysfunctional phenotypes. Here, we show that induction of endoplasmic reticulum (ER) stress in stem cell-derived alpha (SC-α) cells induces hypersecretion of glucagon. ER stress also increases the secretion of glicentin and the expression of glucagon-like peptide-1 (GLP-1), peptides produced by alternate cleavage of proglucagon by the prohormone convertase 1 (PC1/3) enzyme. Additionally, ER stress establishes a diabetic transcriptional state in SC

SUBMITTER: Shrestha S 

PROVIDER: S-EPMC12181959 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature