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RyR2/IRBIT regulates insulin gene transcription, insulin content, and secretion in the insulinoma cell line INS-1

ABSTRACT: The role of ER Ca2+ release via ryanodine receptors (RyR) in pancreatic B-cell function is not well defined. Deletion of RyR2 from the rat insulinoma INS-1 enhanced the Ca2+ integral (AUC) stimulated by glucose, and reduced levels of the protein IRBIT (AHCYL1). Deletion of IRBIT increased the Ca2+ AUC in response to glucose via enhanced IP3 receptor activity. Insulin content, basal and glucose-stimulated insulin secretion (GSIS), and INS2 mRNA levels were reduced in both RyR2KO and IRBITKO cells. Nuclear localization of S-adenosylhomocysteinase (AHCY) was increased in RyR2KO and IRBITKO cells, and exon 2 of the INS1 and INS2 genes was more extensively methylated in RyR2KO and IRBITKO cells. Deletion of RyR2 or IRBIT resulted in differential regulation of 314 and 137 proteins, respectively, with 41 in common. We conclude that RyR2 regulates IRBIT levels in INS-1 cells, and together regulate insulin content, GSIS, and the proteome, perhaps via DNA methylation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Rattus Norvegicus (ncbitaxon:10116)

SUBMITTER: Gregory Hockerman

PROVIDER: MSV000088344 | MassIVE | Wed Nov 10 10:19:00 GMT 2021

REPOSITORIES: MassIVE

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