Stimulation of insulin secretion induced by low 4-cresol dose involves the RPS6KA3 signalling pathway.

ABSTRACT: 4-cresol (4-methylphenol, p-cresol) is a xenobiotic substance negatively correlated with type 2 diabetes and associated with health improvement in preclinical models of diabetes. We aimed at refining our understanding of the physiological role of this metabolite and identifying potential signalling mechanisms. Functional studies revealed that 4-cresol does not deteriorate insulin sensitivity in human primary adipocytes and exhibits an additive effect to that of insulin on insulin sensitivity in mouse C2C12 myoblasts. Experiments in mouse isolated islets showed that 4-cresol potentiates glucose induced insulin secretion. We demonstrated the absence of off target effects of 4-cresol on a panel of 44 pharmacological compounds. Screening large panels of 241 G protein-coupled receptors (GPCRs)

SUBMITTER: Brial F 

PROVIDER: S-EPMC11500888 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature