{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:23:59Z","timestamp":1789683839127,"version":"4.0.1"},"reference-count":35,"publisher":"American Diabetes Association","issue":"12","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":2844,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:p>Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. \u03b2-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo \u03b2-cell insulin secretion and decreased \u03b2-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow\u2013fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to \u03b2-cell dysfunction.<\/jats:p>","DOI":"10.2337\/db13-0314","type":"journal-article","created":{"date-parts":[[2013,9,6]],"date-time":"2013-09-06T00:22:20Z","timestamp":1378426940000},"page":"4201-4207","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":45,"title":["Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs \u03b2-Cell Function"],"prefix":"10.2337","volume":"62","author":[{"given":"Giovanna","family":"Muscogiuri","sequence":"first","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam B.","family":"Salmon","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies, San Antonio, Texas"},{"name":"Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Aguayo-Mazzucato","sequence":"additional","affiliation":[{"name":"Section on Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Li","sequence":"additional","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Balas","sequence":"additional","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolfo","family":"Guardado-Mendoza","sequence":"additional","affiliation":[{"name":"Diabetes Division, University of Texas Health Science Center, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Giaccari","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolic Diseases, Universit\u00e0 Cattolica del Sacro Cuore, Policlinico \u201cA. 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