Oxidative stress and calcium dysregulation by palmitate in type 2 diabetes.
- Ly LD Department of Physiology, Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Gangwon-Do, Republic of Korea.
- Xu S Department of Physiology, Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Gangwon-Do, Republic of Korea.
- Choi SK Department of Physiology, Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Gangwon-Do, Republic of Korea.
- Ha CM Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
- Thoudam T Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
- Cha SK Department of Physiology, Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Gangwon-Do, Republic of Korea.
- Wiederkehr A Mitochondrial Function, Nestlé Institute of Health Sciences, Lausanne, Switzerland.
- Wollheim CB Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
- Lee IK Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea.
- Park KS Department of Physiology, Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Gangwon-Do, Republic of Korea.
- 2017-02-04
Published in:
- Experimental & molecular medicine. - 2017
Animals
CD36 Antigens
Calcium
Diabetes Mellitus, Type 2
Endoplasmic Reticulum
Endoplasmic Reticulum Stress
Fatty Acids, Nonesterified
Humans
Insulin-Secreting Cells
Mitochondria
Oxidative Stress
Palmitic Acids
Reactive Oxygen Species
English
Free fatty acids (FFAs) are important substrates for mitochondrial oxidative metabolism and ATP synthesis but also cause serious stress to various tissues, contributing to the development of metabolic diseases. CD36 is a major mediator of cellular FFA uptake. Inside the cell, saturated FFAs are able to induce the production of cytosolic and mitochondrial reactive oxygen species (ROS), which can be prevented by co-exposure to unsaturated FFAs. There are close connections between oxidative stress and organellar Ca2+ homeostasis. Highly oxidative conditions induced by palmitate trigger aberrant endoplasmic reticulum (ER) Ca2+ release and thereby deplete ER Ca2+ stores. The resulting ER Ca2+ deficiency impairs chaperones of the protein folding machinery, leading to the accumulation of misfolded proteins. This ER stress may further aggravate oxidative stress by augmenting ER ROS production. Secondary to ER Ca2+ release, cytosolic and mitochondrial matrix Ca2+ concentrations can also be altered. In addition, plasmalemmal ion channels operated by ER Ca2+ depletion mediate persistent Ca2+ influx, further impairing cytosolic and mitochondrial Ca2+ homeostasis. Mitochondrial Ca2+ overload causes superoxide production and functional impairment, culminating in apoptosis. This vicious cycle of lipotoxicity occurs in multiple tissues, resulting in β-cell failure and insulin resistance in target tissues, and further aggravates diabetic complications.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1038/emm.2016.157
- PMID 28154371
- Persistent URL
- https://sonar.ch/global/documents/43477
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