{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:40:45Z","timestamp":1790041245673,"version":"4.0.1"},"reference-count":41,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants & Redox Signaling"],"published-print":{"date-parts":[[2016,1]]},"abstract":"\n \n Aims:<\/jats:italic>\n <\/jats:bold>\n To investigate the regulation of hepatic glucose production by cystathionine \u03b3-lyase (CSE)-generated hydrogen sulfide (H\n 2<\/jats:sub>\n S) in hepatic glucose production under physiological conditions.\n \n Results:<\/jats:italic>\n <\/jats:bold>\n We found that CSE knockout (KO) mice had a reduced rate of gluconeogenesis, which was reversed by administration of NaHS (an H\n 2<\/jats:sub>\n S donor) (i.p.). Interestingly, isolated CSE KO hepatocytes exhibited a reduced glycemic response to chemical-induced activation of the cyclic adenosine monophosphate (cAMP)\/protein kinase A (PKA) and glucocorticoid pathways compared with wild-type (WT) hepatocytes. Treatment with the inhibitors for PKA (KT5720) or glucocorticoid receptor (GR) (RU-486) significantly reduced H\n 2<\/jats:sub>\n S-stimulated glucose production from both WT and CSE KO mouse hepatocytes. NaHS treatment upregulated the protein levels of key gluconeogenic transcription factors, such as peroxisome proliferator-activated receptor-\u03b3 coactivator-1\u03b1 (PGC-1\u03b1) and CCAAT-enhancer-binding protein-\u03b2 (C\/EBP-\u03b2). Moreover, exogenous H\n 2<\/jats:sub>\n S augmented the S-sulfhydration of the rate-limiting gluconeogenic enzymes and PGC-1\u03b1 and increased their activities, which were lower in untreated CSE KO hepatocytes. Finally, knockdown of PGC-1\u03b1, but not C\/EBP-\u03b2, significantly decreased NaHS-induced glucose production from the primary hepatocytes.\n \n Innovation:<\/jats:italic>\n <\/jats:bold>\n This study demonstrates the stimulatory effect of endogenous H\n 2<\/jats:sub>\n S on liver glucose production and reveals three underlying mechanisms; that is, H\n 2<\/jats:sub>\n S upregulates the expression levels of PGC-1\u03b1 and phosphoenolpyruvate carboxykinase\n via<\/jats:italic>\n the GR pathway; H\n 2<\/jats:sub>\n S upregulates the expression level of PGC-1\u03b1 through the activation of the cAMP\/PKA pathway as well as PGC-1\u03b1 activity\n via<\/jats:italic>\n S-sulfhydration; and H\n 2<\/jats:sub>\n S upregulates the expression and the activities (by S-sulfhydration) of glucose-6-phosphatase and fructose-1,6-bisphosphatase.\n \n Conclusion:<\/jats:italic>\n <\/jats:bold>\n This study may offer clues for the homeostatic regulation of glucose metabolism under physiological conditions and its dysregulation in metabolic syndrome.\n Antioxid. Redox Signal.<\/jats:italic>\n 24, 129\u2013140.\n <\/jats:p>","DOI":"10.1089\/ars.2015.6369","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T16:41:04Z","timestamp":1443112864000},"page":"129-140","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":62,"title":["Decreased Gluconeogenesis in the Absence of Cystathionine Gamma-Lyase and the Underlying Mechanisms"],"prefix":"10.1177","volume":"24","author":[{"given":"Ashley A.","family":"Untereiner","sequence":"first","affiliation":[{"name":"Lakehead University","place":["Canada"]},{"name":"Lakehead University","place":["Canada"]},{"name":"Thunder Bay Regional Research Institute","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Lakehead University","place":["Canada"]},{"name":"Laurentian University","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YoungJun","family":"Ju","sequence":"additional","affiliation":[{"name":"Lakehead University","place":["Canada"]},{"name":"Lakehead University","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Lakehead University","place":["Canada"]},{"name":"Lakehead University","place":["Canada"]},{"name":"Thunder Bay Regional Research Institute","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,1,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.19.13033"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.44.3.267"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.209783"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0627"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.01.059"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27794"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115634109"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(89)90105-4"},{"key":"e_1_3_3_10_2","first-page":"788","volume-title":"Methods of Enzymatic Analysis","author":"Harper AE","year":"1963","unstructured":"Harper AE. 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