| Autor: |
Mohan, Ramkumar, Jo, Seokwon, Da Sol Chung, Elina, Oribamise, Eunice, Lockridge, Amber, Abrahante-Lloréns, Juan E., Ruan, Hai-Bin, Yang, Xiao-Yong, Alejandro, Emilyn U. |
| Předmět: |
|
| Zdroj: |
Cells (2073-4409); Oct2021, Vol. 10 Issue 10, p2801-2801, 1p |
| Abstrakt: |
The nutrient-sensor O-GlcNAc transferase (Ogt), the sole enzyme that adds an O-GlcNAc-modification onto proteins, plays a critical role for pancreatic β-cell survival and insulin secretion. We hypothesized that β-cell Ogt overexpression would confer protection from β-cell failure in response to metabolic stressors, such as high-fat diet (HFD) and streptozocin (STZ). Here, we generated a β-cell-specific Ogt in overexpressing (βOgtOE) mice, where a significant increase in Ogt protein level and O-GlcNAc-modification of proteins were observed in islets under a normal chow diet. We uncovered that βOgtOE mice show normal peripheral insulin sensitivity and glucose tolerance with a regular chow diet. However, when challenged with an HFD, only female βOgtOE (homozygous) Hz mice developed a mild glucose intolerance, despite increased insulin secretion and normal β-cell mass. While female mice are normally resistant to low-dose STZ treatments, the βOgtOE Hz mice developed hyperglycemia and glucose intolerance post-STZ treatment. Transcriptome analysis between islets with loss or gain of Ogt by RNA sequencing shows common altered pathways involving pro-survival Erk and Akt and inflammatory regulators IL1β and NFkβ. Together, these data show a possible gene dosage effect of Ogt and the importance O-GlcNAc cycling in β-cell survival and function to regulate glucose homeostasis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
