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Hydrogen Sulfide Donor NaHS Improves Metabolism and Reduces Muscle Atrophy in Type 2 Diabetes: Implication for Understanding Sarcopenic Pathophysiology
Joint Authors
Al Madhoun, Ashraf
Al-Mulla, Fahd
Arefanian, Hossein
Bitar, Milad S.
Nader, Joelle
Al-Ali, Waleed
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-10-30
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Sarcopenia, a loss of muscle mass and functionality, constitutes a major contributor to disability in diabetes.
Hydrogen sulfide (H2S) dynamics and muscle mass regulatory signaling were studied in GK rats, a model for type 2 diabetes (T2D).
GK rats exhibited a number of features that are consistent with sarcopenia and T2D including loss of muscle mass and strength, in addition to glucose intolerance, insulin resistance, and impaired β-cell responsiveness to glucose.
Mechanistically, activation levels of Akt, a key modulator of protein balance, were decreased in T2D.
Consequently, we confirmed reduced activity of mTOR signaling components and higher expression of atrophy-related markers typified by FoxO1/atrogin-1/MuRF1 and myostatin-Smad2/3 signaling during the course of diabetes.
We observed in GK rat reduced antioxidant capacity (↓GSH/GSSG) and increased expression and activity of NADPH oxidase in connection with augmented rate of oxidation of lipids, proteins, and DNA.
H2S bioavailability and the expression of key enzymes involved in its synthesis were suppressed as a function of diabetes.
Interestingly, GK rats receiving NaHS displayed increased muscle Akt/mTOR signaling and decreased expression of myostatin and the FoxO1/MuRF1/atrogin-dependent pathway.
Moreover, diabetes-induced heightened state of oxidative stress was also ameliorated in response to NaHS therapy.
Overall, the current data support the notion that a relationship exists between sarcopenia, heightened state of oxidative stress, and H2S deficiency at least in the context of diabetes.
Moreover, treatment with a potent H2S donor at an early stage of diabetes is likely to mitigate the development of sarcopenia/frailty and predictably reduces its devastating sequelae of amputation.
American Psychological Association (APA)
Bitar, Milad S.& Nader, Joelle& Al-Ali, Waleed& Al Madhoun, Ashraf& Arefanian, Hossein& Al-Mulla, Fahd. 2018. Hydrogen Sulfide Donor NaHS Improves Metabolism and Reduces Muscle Atrophy in Type 2 Diabetes: Implication for Understanding Sarcopenic Pathophysiology. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-17.
https://search.emarefa.net/detail/BIM-1211871
Modern Language Association (MLA)
Bitar, Milad S.…[et al.]. Hydrogen Sulfide Donor NaHS Improves Metabolism and Reduces Muscle Atrophy in Type 2 Diabetes: Implication for Understanding Sarcopenic Pathophysiology. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-17.
https://search.emarefa.net/detail/BIM-1211871
American Medical Association (AMA)
Bitar, Milad S.& Nader, Joelle& Al-Ali, Waleed& Al Madhoun, Ashraf& Arefanian, Hossein& Al-Mulla, Fahd. Hydrogen Sulfide Donor NaHS Improves Metabolism and Reduces Muscle Atrophy in Type 2 Diabetes: Implication for Understanding Sarcopenic Pathophysiology. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-17.
https://search.emarefa.net/detail/BIM-1211871
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211871