Genetic Ablation of the Nutrient Sensor Ogt in Endocrine Progenitors Is Dispensable for β-Cell Development but Essential for Maintenance of β-Cell Mass.

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.

SUBMITTER: Wong A 

PROVIDER: S-EPMC9855876 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature