Abstract
Previously we utilized a murine model to demonstrate that Ogt deletion in pancreatic progenitors (OgtKO(Panc)) causes pancreatic hypoplasia, partly mediated by a reduction in the Pdx1-expressing pancreatic progenitor pool. Here, we continue to explore the role of Ogt in pancreas development by deletion of Ogt in the endocrine progenitors (OgtKO(Endo)). At birth OgtKO(Endo), were normoglycemic and had comparable pancreas weight and α-cell, and β-cell mass to littermate controls. At postnatal day 23, OgtKO(Endo) displayed wide ranging but generally elevated blood glucose levels, with histological analyses showing aberrant islet architecture with α-cells invading the islet core. By postnatal day 60, these mice were overtly diabetic and showed significant loss of both α-cell and β-cell mass. Together, these results highlight the indispensable role of Ogt in maintenance of β-cell mass and glucose homeostasis.