Raptor levels are critical for ß-cell adaptation to a high-fat diet in male mice.
Mol Metab
; 75: 101769, 2023 09.
Article
in En
| MEDLINE
| ID: mdl-37423392
ABSTRACT
OBJECTIVE:
The essential role of raptor/mTORC1 signaling in ß-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the role of mTORC1 function in adaptation of ß-cells to insulin resistant state.METHOD:
Here, we use mice with heterozygous deletion of raptor in ß-cells (ßraHet) to assess whether reduced mTORC1 function is critical for ß-cell function in normal conditions or during ß-cell adaptation to high-fat diet (HFD).RESULTS:
Deletion of a raptor allele in ß-cells showed no differences at the metabolic level, islets morphology, or ß-cell function in mice fed regular chow. Surprisingly, deletion of only one allele of raptor increases apoptosis without altering proliferation rate and is sufficient to impair insulin secretion when fed a HFD. This is accompanied by reduced levels of critical ß-cell genes like Ins1, MafA, Ucn3, Glut2, Glp1r, and specially PDX1 suggesting an improper ß-cell adaptation to HFD.CONCLUSION:
This study identifies that raptor levels play a key role in maintaining PDX1 levels and ß-cell function during the adaptation of ß-cell to HFD. Finally, we identified that Raptor levels regulate PDX1 levels and ß-cell function during ß-cell adaptation to HFD by reduction of the mTORC1-mediated negative feedback and activation of the AKT/FOXA2/PDX1 axis. We suggest that Raptor levels are critical to maintaining PDX1 levels and ß-cell function in conditions of insulin resistance in male mice.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
/
Insulin-Secreting Cells
Limits:
Animals
Language:
En
Journal:
Mol Metab
Year:
2023
Document type:
Article