NYMC Faculty Publications
TRAIL Induces Proliferation in Rodent Pancreatic Beta Cells via AKT Activation
Author Type(s)
Faculty
DOI
10.1530/JME-20-0037
Journal Title
Journal of Molecular Endocrinology
First Page
325
Last Page
338
Document Type
Article
Publication Date
5-11-2021
Department
Pharmacology
Abstract
Strategies to increase functional pancreatic beta cell mass is of great interest in diabetes-related research. TNF-related apoptosis-inducing ligand (TRAIL) is well known to promote proliferation and survival in various cell types, including vascular smooth muscle and endothelial cells. Correlation between the protective nature of TRAIL on these cells and its proliferative effect is noteworthy. TRAIL's seemingly protective/therapeutic effect in diabetes prompted us to question whether it may act as an inducer of proliferation in pancreatic beta cells. We used rat primary islet cells and MIN6 mouse beta cell line to investigate TRAIL-induced proliferation. Cell viability and/or death was analyzed by MTT, WST-1, and Annexin-V/PI assays, while proliferation rates and pathways were assessed via immunocytochemical and Western blot analyses. Receptor neutralization antibodies identified the mediator receptors. Recombinant soluble TRAIL (sTRAIL) treatment led to 1.6-fold increased proliferation in insulin-positive cells in dispersed rat islets compared to the untreated group, while adenovirus-mediated overexpression of TRAIL increased the number of proliferating beta cells up to more than six-fold. sTRAIL or adenoviral vector-mediated TRAIL overexpression induced proliferation in MIN6 cells also. TRAIL's proliferative effect was mediated via AKT activation, which was suppressed upon specific inhibition. Neutralization of each TRAIL receptor reversed the proliferative effect to some degree, with the highest level of inhibition in death receptor 5 (DR5) blockage in MIN6 cells and in decoy receptor 1 (DcR1) blockage in primary rat beta cells. Thus, TRAIL induces proliferation in rodent pancreatic beta cells through activation of the AKT pathway.
Recommended Citation
Kahraman, S., Yilmaz, O., Altunbas, H., Dirice, E., & Sanlioglu, A. (2021). TRAIL Induces Proliferation in Rodent Pancreatic Beta Cells via AKT Activation. Journal of Molecular Endocrinology, 66 (4), 325-338. https://doi.org/10.1530/JME-20-0037