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

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 higher insulin levels in renal failure are due to decreased clearance of insulin caused by reduced renal function. However, here we showed that accumulation of the gut microbiota-derived uremic toxin phenyl sulfate in renal failure stimulates insulin secretion from the pancreas and induces insulin resistance in adipocytes. These data suggest that the accumulation of uremic toxins modulates glucose metabolism in CKD and DKD patients. This result also reveals a new insulin secretion mechanism and will be a clue for developing new anti-diabetic interventions.