BCL-XL Overexpression Protects Pancreatic ß-Cells against Cytokine- and Palmitate-Induced Apoptosis.
Int J Mol Sci
; 24(6)2023 Mar 16.
Article
in En
| MEDLINE
| ID: mdl-36982731
ABSTRACT
Diabetes is a chronic disease that affects glucose metabolism, either by autoimmune-driven ß-cell loss or by the progressive loss of ß-cell function, due to continued metabolic stresses. Although both α- and ß-cells are exposed to the same stressors, such as proinflammatory cytokines and saturated free fatty acids (e.g., palmitate), only α-cells survive. We previously reported that the abundant expression of BCL-XL, an anti-apoptotic member of the BCL-2 family of proteins, is part of the α-cell defense mechanism against palmitate-induced cell death. Here, we investigated whether BCL-XL overexpression could protect ß-cells against the apoptosis induced by proinflammatory and metabolic insults. For this purpose, BCL-XL was overexpressed in two ß-cell lines-namely, rat insulinoma-derived INS-1E and human insulin-producing EndoC-ßH1 cells-using adenoviral vectors. We observed that the BCL-XL overexpression in INS-1E cells was slightly reduced in intracellular Ca2+ responses and glucose-stimulated insulin secretion, whereas these effects were not observed in the human EndoC-ßH1 cells. In INS-1E cells, BCL-XL overexpression partially decreased cytokine- and palmitate-induced ß-cell apoptosis (around 40% protection). On the other hand, the overexpression of BCL-XL markedly protected EndoC-ßH1 cells against the apoptosis triggered by these insults (>80% protection). Analysis of the expression of endoplasmic reticulum (ER) stress markers suggests that resistance to the cytokine and palmitate conferred by BCL-XL overexpression might be, at least in part, due to the alleviation of ER stress. Altogether, our data indicate that BCL-XL plays a dual role in ß-cells, participating both in cellular processes related to ß-cell physiology and in fostering survival against pro-apoptotic insults.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cytokines
/
Insulin-Secreting Cells
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2023
Document type:
Article
Affiliation country: