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Published on: November 11, 2016
Circadian Clock and Sirtuins in Diabetic Lung: A Mechanistic Perspective
Shuang Zhou1, Yi-Min Dai2, Xiao-Feng Zeng1
1Department of Rheumatology, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Abstract:
Diabetes-induced tissue injuries in target organs such as the kidney, heart, eye, liver, skin, and nervous system contribute significantly to the morbidity and mortality of diabetes. However, whether the lung should be considered a diabetic target organ has been discussed for decades. Accumulating evidence shows that both pulmonary histological changes and functional abnormalities have been observed in diabetic patients, suggesting that the lung is a diabetic target organ. Mechanisms underlying diabetic lung are unclear, however, oxidative stress, systemic inflammation, and premature aging convincingly contribute to them. Circadian system and Sirtuins have been well-documented to play important roles in above mechanisms. Circadian rhythms are intrinsic mammalian biological oscillations with a period of near 24 h driven by the circadian clock system. This system plays an important role in the regulation of energy metabolism, oxidative stress, inflammation, cellular proliferation and senescence, thus impacting metabolism-related diseases, chronic airway diseases and cancers. Sirtuins, a family of adenine dinucleotide (NAD+)-dependent histone deacetylases, have been demonstrated to regulate a series of physiological processes and affect diseases such as obesity, insulin resistance, type 2 diabetes (T2DM), heart disease, cancer, and aging. In this review, we summarize recent advances in the understanding of the roles of the circadian clock and Sirtuins in regulating cellular processes and highlight the potential interactions of the circadian clock and Sirtuins in the context of diabetic lung.
Insights
Diabetes affects the lungs, causing tissue damage. This review explores how the circadian clock and Sirtuins may influence diabetic lung disease development.
Area of Science:
- Endocrinology and Metabolism
- Pulmonology
- Molecular Biology
Background:
- Diabetes mellitus is a systemic disease causing target organ damage, including potential lung complications.
- The lung's role as a diabetic target organ is increasingly recognized, with observed histological and functional changes in patients.
- Mechanisms like oxidative stress, inflammation, and aging are implicated in diabetic lung disease.
Purpose of the Study:
- To review the current understanding of the circadian clock system's role in diabetic lung pathophysiology.
- To examine the involvement of Sirtuins in the mechanisms underlying diabetic lung complications.
- To explore the interplay between the circadian clock and Sirtuins in the context of diabetes-related lung disease.
Main Methods:
- Literature review of recent advances in circadian biology and Sirtuin research.
- Analysis of studies investigating the impact of diabetes on pulmonary health.
- Synthesis of evidence linking circadian rhythms and Sirtuins to oxidative stress, inflammation, and aging in diabetes.
Main Results:
- The circadian clock system regulates key cellular processes, including metabolism, oxidative stress, and inflammation, relevant to diabetic complications.
- Sirtuins, NAD+-dependent deacetylases, are crucial regulators of metabolic health, aging, and disease, including diabetes.
- Evidence suggests that disruptions in circadian rhythms and altered Sirtuin activity contribute to diabetic lung injury.
Conclusions:
- The circadian clock and Sirtuins are critical regulators of cellular homeostasis and are implicated in the pathogenesis of diabetic lung disease.
- Understanding the interaction between the circadian system and Sirtuins offers potential therapeutic targets for managing diabetic lung complications.
- Further research is warranted to elucidate the precise molecular mechanisms governing the circadian clock and Sirtuin pathways in diabetic lung injury.
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