Hyperaminoacidemia from interrupted glucagon signaling increases pancreatic acinar cell proliferation and size via mTORC1 and YAP pathways.

ABSTRACT: Increased blood amino acid levels (hyperaminoacidemia) stimulate pancreas expansion by unclear mechanisms. Here, by genetic and pharmacological disruption of glucagon receptor (GCGR) in mice and zebrafish, we found that the ensuing hyperaminoacidemia promotes pancreatic acinar cell proliferation and cell hypertrophy, which can be mitigated by a low protein diet in mice. In addition to mammalian target of rapamycin complex 1 (mTORC1) signaling, acinar cell proliferation required slc38a5, the most highly expressed amino acid transporter gene in both species. Transcriptomics data revealed the activation signature of yes-associated protein (YAP) in acinar cells of mice with hyperaminoacidemia, consistent with the observed increase in YAP-expressing acinar cells. Yap1 activation also occ

SUBMITTER: Dai C 

PROVIDER: S-EPMC11667045 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature