{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:32:59Z","timestamp":1792006379753,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T00:00:00Z","timestamp":1434499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Mid-Atlantic Nutrition Obesity Research Center","award":["NIH DK072488"],"award-info":[{"award-number":["NIH DK072488"]}]},{"name":"Baltimore Diabetes Research and Training Center","award":["NIH P60-DK-079637"],"award-info":[{"award-number":["NIH P60-DK-079637"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["No. 81100613"],"award-info":[{"award-number":["No. 81100613"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alanine transaminase (ALT) plays an important role in gluconeogenesis by converting alanine into pyruvate for glucose production. Early studies have shown that ALT activities are upregulated in gluconeogenic conditions and may be implicated in the development of diabetes. ALT consists of two isoforms, ALT1 and ALT2, with distinctive subcellular and tissue distributions. Whether and how they are regulated are largely unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>By using Western blotting analysis, we measured hepatic ALT isoforms at the protein level in obese and diabetic animals and in Fao hepatoma cells treated with dexamethasone and insulin. In addition, we measured glucose output in Fao cells over\u2010expressing ALT1 and ALT2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both ALT isoforms in the liver were increased in diabetic Goto\u2010Kakizaki rats and during fasting. However, in ob\/ob mice, only ALT2, but not ALT1, protein levels were elevated, and the increase of ALT2 was correlated with that of ALT activity. We further demonstrated that, <jats:italic>in vitro<\/jats:italic>, both ALT1 and ALT2 were induced by glucocorticoid dexamethasone, but suppressed by insulin in Fao cells. Finally, we showed that the over\u2010expression of ALT1 and ALT2 in Fao cells directly increased glucose output.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We have shown the similarity and difference in the regulation of ALT isoforms in gluconeogenic conditions at the protein level, supporting that ALT isoenzymes play an important role in glucose metabolism and may be implicated the development of insulin resistance and diabetes. Copyright \u00a9 2015 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dmrr.2655","type":"journal-article","created":{"date-parts":[[2015,4,11]],"date-time":"2015-04-11T03:48:51Z","timestamp":1428724131000},"page":"562-571","source":"Crossref","is-referenced-by-count":82,"title":["Hepatic ALT isoenzymes are elevated in gluconeogenic conditions including diabetes and suppressed by insulin at the protein level"],"prefix":"10.1002","volume":"31","author":[{"given":"Kun","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine University of Maryland School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine University of Maryland School of Medicine  Baltimore MD USA"},{"name":"Department of Endocrinology and Metabolism Disease Kunshan Hospital of Jiangsu University  Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keming","family":"Xie","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine University of Maryland School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daozhan","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine University of Maryland School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongze","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine University of Maryland School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Wei","family":"Gong","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Nutrition, Department of Medicine University of Maryland School of Medicine  Baltimore MD USA"},{"name":"VA Research Service, Geriatric Research, Education and Clinical Center Baltimore Veterans Administration Medical Center  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,17]]},"reference":[{"issue":"4","key":"e_1_2_8_2_1","first-page":"E709","article-title":"Glucose production, recycling, and gluconeogenesis in normals and diabetics: a mass isotopomer [U\u201013C]glucose study","volume":"270","author":"Tayek JA","year":"1996","journal-title":"Am J Physiol"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(98)00162-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1776"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0320195"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(73)90269-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0950-351X(05)80207-1"},{"issue":"3","key":"e_1_2_8_8_1","first-page":"476","article-title":"Glucocorticosteroids and transaminase activity I. 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