Journal article
Breaking the Feedback Loop of β-Cell Failure: Insight into the Pancreatic β-Cell’s ER-Mitochondria Redox Balance
Cells (Basel, Switzerland), Vol.14(6), 399
03/08/2025
DOI: 10.3390/cells14060399
PMCID: PMC11941261
PMID: 40136648
Abstract
Pancreatic β-cells rely on a delicate balance between the endoplasmic reticulum (ER) and mitochondria to maintain sufficient insulin stores for the regulation of whole animal glucose homeostasis. The ER supports proinsulin maturation through oxidative protein folding, while mitochondria supply the energy and redox buffering that maintain ER proteostasis. In the development of Type 2 diabetes (T2D), the progressive decline of β-cell function is closely linked to disruptions in ER-mitochondrial communication. Mitochondrial dysfunction is a well-established driver of β-cell failure, whereas the downstream consequences for ER redox homeostasis have only recently emerged. This interdependence of ER-mitochondrial functions suggests that an imbalance is both a cause and consequence of metabolic dysfunction. In this review, we discuss the regulatory mechanisms of ER redox control and requirements for mitochondrial function. In addition, we describe how ER redox imbalances may trigger mitochondrial dysfunction in a vicious feed forward cycle that accelerates β-cell dysfunction and T2D onset.
Details
- Title: Subtitle
- Breaking the Feedback Loop of β-Cell Failure: Insight into the Pancreatic β-Cell’s ER-Mitochondria Redox Balance
- Creators
- Amira Zaher - University of IowaSamuel B. Stephens - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cells (Basel, Switzerland), Vol.14(6), 399
- DOI
- 10.3390/cells14060399
- PMID
- 40136648
- PMCID
- PMC11941261
- NLM abbreviation
- Cells
- ISSN
- 2073-4409
- eISSN
- 2073-4409
- Publisher
- MDPI
- Grant note
- Breakthrough T1DNational Institutes of Health: R01 DK140093 US Department of Defense: W81XWH-20-1-200
This work was supported by Breakthrough T1D (SRA-2024-1553), the National Institutes of Health (R01 DK140093), and the US Department of Defense (W81XWH-20-1-200) to S.B.S.
- Language
- English
- Date published
- 03/08/2025
- Academic Unit
- Anatomy and Cell Biology; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984799674702771
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