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Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) 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 <jats:italic>\u03b2<\/jats:italic>\u2010cell 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\u2010related markers typified by FoxO1\/atrogin\u20101\/MuRF1 and myostatin\u2010Smad2\/3 signaling during the course of diabetes. We observed in GK rat reduced antioxidant capacity (\u2193GSH\/GSSG) and increased expression and activity of NADPH oxidase in connection with augmented rate of oxidation of lipids, proteins, and DNA. H<jats:sub>2<\/jats:sub>S 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\u2010dependent pathway. Moreover, diabetes\u2010induced 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 H<jats:sub>2<\/jats:sub>S deficiency at least in the context of diabetes. Moreover, treatment with a potent H<jats:sub>2<\/jats:sub>S donor at an early stage of diabetes is likely to mitigate the development of sarcopenia\/frailty and predictably reduces its devastating sequelae of amputation.<\/jats:p>","DOI":"10.1155\/2018\/6825452","type":"journal-article","created":{"date-parts":[[2018,10,30]],"date-time":"2018-10-30T23:31:19Z","timestamp":1540942279000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Hydrogen Sulfide Donor NaHS Improves Metabolism and Reduces Muscle Atrophy in Type 2 Diabetes: Implication for Understanding Sarcopenic Pathophysiology"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0308-1662","authenticated-orcid":false,"given":"Milad S.","family":"Bitar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3699-1187","authenticated-orcid":false,"given":"Joelle","family":"Nader","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waleed","family":"Al-Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashraf","family":"Al Madhoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hossein","family":"Arefanian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahd","family":"Al-Mulla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,30]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2003.09.012"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2005.11.004"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12365"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2743"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejvs.2007.05.018"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002938"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afq034"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1166"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2310"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/fampra\/cmr054"},{"key":"e_1_2_9_11_2","first-page":"39","article-title":"Pharmacological interventions on critical limb ischemia in diabetic patients","volume":"53","author":"Parekh N.","year":"2012","journal-title":"The Journal of Cardiovascular Surgery"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2014.10.094"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.49"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0366-6999.20122485"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.07.026"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004180050286"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105121108"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2014.11.012"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4507"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.179333"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-8-53"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00189.2013"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.017145"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280883"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2006.11.024"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00047.2011"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6738701"},{"key":"e_1_2_9_28_2","first-page":"229","article-title":"Increased lipid peroxidation in tissues of nickel chloride-treated rats","volume":"15","author":"Sunderman F. 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