| First Author | Mohan R | Year | 2021 |
| Journal | Diabetes | Volume | 70 |
| Issue | 11 | Pages | 2608-2625 |
| PubMed ID | 34462257 | Mgi Jnum | J:331771 |
| Mgi Id | MGI:7398341 | Doi | 10.2337/db21-0468 |
| Citation | Mohan R, et al. (2021) OGT Regulates Mitochondrial Biogenesis and Function via Diabetes Susceptibility Gene Pdx1. Diabetes 70(11):2608-2625 |
| abstractText | O-GlcNAc transferase (OGT), a nutrient sensor sensitive to glucose flux, is highly expressed in the pancreas. However, the role of OGT in the mitochondria of beta-cells is unexplored. In this study, we identified the role of OGT in mitochondrial function in beta-cells. Constitutive deletion of OGT (betaOGTKO) or inducible ablation in mature beta-cells (ibetaOGTKO) causes distinct effects on mitochondrial morphology and function. Islets from betaOGTKO, but not ibetaOGTKO, mice display swollen mitochondria, reduced glucose-stimulated oxygen consumption rate, ATP production, and glycolysis. Alleviating endoplasmic reticulum stress by genetic deletion of Chop did not rescue the mitochondrial dysfunction in betaOGTKO mice. We identified altered islet proteome between betaOGTKO and ibetaOGTKO mice. Pancreatic and duodenal homeobox 1 (Pdx1) was reduced in in betaOGTKO islets. Pdx1 overexpression increased insulin content and improved mitochondrial morphology and function in betaOGTKO islets. These data underscore the essential role of OGT in regulating beta-cell mitochondrial morphology and bioenergetics. In conclusion, OGT couples nutrient signal and mitochondrial function to promote normal beta-cell physiology. |
