{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:03:59Z","timestamp":1773299039635,"version":"3.50.1"},"reference-count":0,"publisher":"American Diabetes Association","issue":"5","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1996,5,1]]},"abstract":"<jats:p>We studied the effects of fatty acid oxidation on insulin secretion of db\/db mice and underlying molecular mechanisms of these effects. At 2\u20133 months of age, db\/db mice were markedly obese, hyperglycemic, and hyperinsulinemic. Serum free fatty acid (FFA) levels were increased in 2-month-old (1.5 \u00b1 0.1 vs. 1.1 \u00b1 0.1 mmol\/l, P &amp;lt; 0.05) and 3-month-old (1.9 \u00b1 0.1 vs. 1.2 \u00b1 0.1 mmol\/l, P &amp;lt; 0.01) mice compared with the age and sex-matched db\/+ mice serving as controls. Glucose-induced insulin release from db\/db islets was markedly decreased compared with that from db\/+ islets and was specifically ameliorated (by 54% in 2-month-old and 38% in 3-month-old mice) by exposure to a carnitine palmitoyltransferase I inhibitor, etomoxir (1 \u03bcmol\/l). Etomoxir failed to affect the insulin response to \u03b1-ketoisocaproate. The effect of etomoxir on glucose-induced insulin release was lost after culturing db\/db islets in RPMI medium containing 22 mmol\/l glucose but no fatty acid. Culture of db\/+ islets with 0.125 mmol\/l palmitate led to a decrease in glucose-induced insulin secretion, which was partially reversible by etomoxir. Both islet glucose oxidation and the ratio of glucose oxidation to utilization were decreased in db\/db islets. Etomoxir significantly enhanced glucose oxidation by 60% and also the ratio of oxidation to glucose utilization (from 27 \u00b1 2.5 to 37 \u00b13.0%, P &amp;lt; 0.05). Pyruvate dehydrogenase (PDH) activity was decreased in islets of db\/db mice (75 \u00b14.2 vs. 91 \u00b1 2.9 nU\/ng DNA, P &amp;lt; 0.01), whereas PDH kinase activity was increased (rate of PDH inactivation \u22120.25 \u00b1 0.02 vs. \u22120.11 \u00b1 0.02\/min, P &amp;lt; 0.01). These abnormalities were partly but not wholly reversed by a 2-h preexposure to etomoxir. In conclusion, elevated FFA levels in the db\/db mouse diminish glucose-induced insulin secretion by a glucose\u2013fatty acid cycle in which fatty acid oxidation inhibits glucose oxidation by decreasing PDH activity and increasing PDH kinase activities.<\/jats:p>","DOI":"10.2337\/diab.45.5.580","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T17:42:54Z","timestamp":1379612574000},"page":"580-586","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":58,"title":["A Fatty Acid\u2014Induced Decrease in Pyruvate Dehydrogenase Activity Is an Important Determinant of \u03b2-Cell Dysfunction in the Obese Diabetic <i>db\/db<\/i> Mouse"],"prefix":"10.2337","volume":"45","author":[{"given":"Yun-Ping","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, The Endocrine and Diabetes Unit, Karolinska Hospital and Institute\u2008S-171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per-Olof","family":"Berggren","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Endocrine and Diabetes Unit, Karolinska Hospital and Institute\u2008S-171 76 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valdemar","family":"Grill","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, The Endocrine and Diabetes Unit, Karolinska Hospital and Institute\u2008S-171 76 Stockholm, Sweden"},{"name":"Endocrine Section, Department of Medicine, University of Trondheim\u2008Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/45\/5\/580\/532962\/45-5-580.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/45\/5\/580\/532962\/45-5-580.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:30:27Z","timestamp":1667406627000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/45\/5\/580\/11078\/A-Fatty-Acid-Induced-Decrease-in-Pyruvate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,5,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1996,5,1]]}},"URL":"https:\/\/doi.org\/10.2337\/diab.45.5.580","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,5,1]]}}}