β-cell adaptation to increased insulin demand is a swift and dynamic process orchestrated by unfolded protein response.
- 1Translational Research Laboratory of Cellular Stress and Adaptation, Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, Romania.
- 2Mohn Research Center for Diabetes Precision Medicine, Department of Clinical Science, University of Bergen, Bergen, Norway.
- 3Translational Research Laboratory of Cellular Stress and Adaptation, Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, Romania. [email protected].
Abstract
Pancreatic β-cells adapt to increased insulin demand through coordinated functional and molecular responses. However, in diabetes, these adaptive pathways eventually fail, driving β-cell dysfunction and demise. One of these pathways is unfolded protein response (UPR), a complex network of sensors and effectors that cooperate to restore endoplasmic reticulum (ER) function under stress. To define the early UPR programs engaged during β-cell adaptation, we employed a murine model of partial β-cell ablation that preserves normoglycemia while imposing an increased secretory workload on the remaining β-cells. Integrating bulk islet transcriptomics with imaging, ultrastructural and physiological analyses, we identified dynamic molecular and functional adaptations during the compensatory phase. The initial transcriptional response was characterised by induction of apoptosis genes and a stress response. This was later replaced by activation of adaptive UPR pathways accompanied by increased insulin processing. Nuclear Atf4 and Xbp1 increased transiently, consistent with engagement of multiple UPR branches through different mechanisms to restore homeostasis. Functionally, partially ablated islets displayed enhanced secretory competence during an acute secondary ER stress challenge, although this adaptive advantage was lost during prolonged stress. Together, these findings define a transient adaptive UPR program that sustains β-cell function during the early response to β-cell loss and provide insight into mechanisms that may be leveraged to enhance β-cell resilience in diabetes.
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BibTeX
@article{daian2026βcell,
title = {{β-cell adaptation to increased insulin demand is a swift and dynamic process orchestrated by unfolded protein response.}},
author = {Laura Maria Daian and Andrei Mircea Vacaru and Gabriela Tanko and Elena Mirela Lamba and Oana-Ana-Maria Mardare and Luiza Ghila and Simona Chera and Ana-Maria Vacaru},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = jul,
doi = {10.1186/s12964-026-03110-9},
url = {https://europepmc.org/article/MED/42928193},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - β-cell adaptation to increased insulin demand is a swift and dynamic process orchestrated by unfolded protein response.
AU - Laura Maria Daian
AU - Andrei Mircea Vacaru
AU - Gabriela Tanko
AU - Elena Mirela Lamba
AU - Oana-Ana-Maria Mardare
AU - Luiza Ghila
AU - Simona Chera
AU - Ana-Maria Vacaru
PY - 2026
DA - 2026/07/29
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03110-9
UR - https://europepmc.org/article/MED/42928193
AB - Pancreatic β-cells adapt to increased insulin demand through coordinated functional and molecular responses. However, in diabetes, these adaptive pathways eventually fail, driving β-cell dysfunction and demise. One of these pathways is unfolded protein response (UPR), a complex network of sensors and effectors that cooperate to restore endoplasmic reticulum (ER) function under stress. To define the early UPR programs engaged during β-cell adaptation, we employed a murine model of partial β-cell ablation that preserves normoglycemia while imposing an increased secretory workload on the remaining β-cells. Integrating bulk islet transcriptomics with imaging, ultrastructural and physiological analyses, we identified dynamic molecular and functional adaptations during the compensatory phase. The initial transcriptional response was characterised by induction of apoptosis genes and a stress response. This was later replaced by activation of adaptive UPR pathways accompanied by increased insulin processing. Nuclear Atf4 and Xbp1 increased transiently, consistent with engagement of multiple UPR branches through different mechanisms to restore homeostasis. Functionally, partially ablated islets displayed enhanced secretory competence during an acute secondary ER stress challenge, although this adaptive advantage was lost during prolonged stress. Together, these findings define a transient adaptive UPR program that sustains β-cell function during the early response to β-cell loss and provide insight into mechanisms that may be leveraged to enhance β-cell resilience in diabetes.
SN - 1478-811X
ER -