Hypoglycemia and hyperinsulinemia induced by phenolic uremic toxins in CKD and DKD patients.

ABSTRACT: Patients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from β-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also f

SUBMITTER: Tongu Y 

PROVIDER: S-EPMC11833073 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature