A selective nonpeptide somatostatin receptor 5 agonist effectively decreases insulin secretion in hyperinsulinism.

ABSTRACT: Congenital hyperinsulinism (HI), a beta cell disorder most commonly caused by inactivating mutations of beta cell K_ATP channels, results in dysregulated insulin secretion and persistent hypoglycemia. Children with K_ATP-HI are unresponsive to diazoxide, the only FDA-approved drug for HI, and utility of octreotide, the second-line therapy, is limited because of poor efficacy, desensitization, and somatostatin receptor type 2 (SST2)-mediated side effects. Selective targeting of SST5, an SST receptor associated with potent insulin secretion suppression, presents a new avenue for HI therapy. Here, we determined that CRN02481, a highly selective nonpeptide SST5 agonist, significantly decreased basal and amino acid-stimulated insulin secretion in both Sur1^-/- (a m

SUBMITTER: Juliana CA 

PROVIDER: S-EPMC10318504 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature