{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:38:28Z","timestamp":1791920308705,"version":"4.3.4"},"reference-count":44,"publisher":"American Diabetes Association","issue":"11","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,11,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Muscle mitochondrial dysfunction occurs in many insulin-resistant states, such as type 2 diabetes, prompting a hypothesis that mitochondrial dysfunction may cause insulin resistance. We determined the impact of insulin deficiency on muscle mitochondrial ATP production by temporarily depriving type 1 diabetic patients of insulin treatment.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014We withdrew insulin for 8.6 \u00b1 0.6 h in nine C-peptide\u2013negative type 1 diabetic subjects and measured muscle mitochondrial ATP production and gene transcript levels (gene array and real-time quantitative PCR) and compared with insulin-treated state. We also measured oxygen consumption (indirect calorimetry); plasma levels of glucagon, bicarbonate, and other substrates; and urinary nitrogen.<\/jats:p>\n               <jats:p>RESULTS\u2014Withdrawal of insulin resulted in increased plasma glucose, branched chain amino acids, nonesterified fatty acids, \u03b2-hydroxybutyrate, and urinary nitrogen but no change in bicarbonate. Insulin deprivation decreased muscle mitochondrial ATP production rate (MAPR) despite an increase in whole-body oxygen consumption and altered expression of many muscle mitochondrial gene transcripts. Transcript levels of genes involved in oxidative phosphorylation were decreased, whereas those involved in vascular endothelial growth factor (VEGF) signaling, inflammation, cytoskeleton signaling, and integrin signaling pathways were increased.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014Insulin deficiency and associated metabolic changes reduce muscle MAPR and expression of oxidative phosphorylation genes in type 1 diabetes despite an increase in whole-body oxygen consumption. Increase in transcript levels of genes involved in VEGF, inflammation, cytoskeleton, and integrin signaling pathways suggest that vascular factors and cell proliferation that may interact with mitochondrial changes occurred.<\/jats:p>","DOI":"10.2337\/db07-0378","type":"journal-article","created":{"date-parts":[[2007,9,5]],"date-time":"2007-09-05T21:00:14Z","timestamp":1189026014000},"page":"2683-2689","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":110,"title":["Effect of Insulin Deprivation on Muscle Mitochondrial ATP Production and Gene Transcript Levels in Type 1 Diabetic Subjects"],"prefix":"10.2337","volume":"56","author":[{"given":"Helen","family":"Karakelides","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism and Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan W.","family":"Asmann","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen L.","family":"Bigelow","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin R.","family":"Short","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketan","family":"Dhatariya","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Coenen-Schimke","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Kahl","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debabrata","family":"Mukhopadhyay","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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