TET-dependent signaling of ß-cell underlies intrauterine hyperglycemia-induced glucose intolerance in offspring [RRBS]

Epidemiologically, gestational diabetes mellitus (GDM) increases offspring's diabetes risk. Intrauterine hyperglycemia (IHG) is a typical characteristic of GDM, impairing offspring's glucose tolerance and insulin secretion, but the underlying mechanisms remain unclear. Here, we found IHG downregulates DNA demethylases Tet2/3 in fetal pancreatic islets. Pancreas-specific Tet2/3 double knockout (DKO) recapitulates the IHG effects. Overall design: To investigate the mechanisms of impairing offspring's glucose tolerance and insulin secretion in IHG offspring. Pancreatic islets from Tet2/3 double knockout mouse was analyzed using RRBS.