{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T11:09:13Z","timestamp":1720350553050},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We aimed at evaluating the impact of short and prolonged mild manipulations of intracellular nitric oxide (NO) bioavailability on the main features of insulin secretion and whether NO promotes mitochondrial biogenesis in isolated \u03b2-cells.<\/jats:p><jats:p>INS-1E \u03b2-cells were exposed to either the intracellular NO donor, hydroxylamine (HA), or the NO synthase inhibitor, L-nitro-arginine-methyl-ester (l-NAME), at concentrations lower than 2.0\u2009mM. Glucose and arginine-induced insulin secretion (GIIS and AIIS) were measured after short (1\u2009h) or prolonged (48\u2009h) exposure to l-NAME 1.0 and 2.0\u2009mM or HA 0.4 and 0.8\u2009mM, lower concentrations were also evaluated for the 1\u2009h effects. Basal insulin secretion (BIS), with either HA or l-NAME added to culture media, and peroxisome proliferators-activated receptor \u03b3 coactivator 1\u03b1 (PGC-1\u03b1), nuclear respiratory factor-1 (NRF-1), and mitochondrial DNA transcription factor-A (Tfam) gene expression during chronic HA supplementation were also measured.<\/jats:p><jats:p>Neither l-NAME nor HA affected insulin release at glucose 3.3\u2009mM or in cell culture (BIS). Both short and prolonged cell exposure to l-NAME potentiated GIIS though with a flat dose-response curve while HA inhibited GIIS only at the highest concentration. AIIS was prevented by short exposure to l-NAME and potentiated by HA, while it did not respond to prolonged incubations. Prolonged cell exposure to HA had no effect on PGC-1\u03b1, NRF-1 or Tfam gene expression.<\/jats:p><jats:p>In INS1E cells an intact NO synthesis is necessary to limit insulin release in response to acute glucose gradients and to fully respond to arginine while intracellular NO enrichment above the physiologic levels further inhibits GIIS and potentiate AIIS only when excessive. Prolonged NO manipulations do not affect AIIS, BIS or mitochondrial biogenesis.<\/jats:p>","DOI":"10.1055\/s-0031-1298015","type":"journal-article","created":{"date-parts":[[2012,2,11]],"date-time":"2012-02-11T00:08:16Z","timestamp":1328918896000},"page":"210-216","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Short and Prolonged Mild Intracellular Nitric Oxide Manipulations on Various Aspects of Insulin Secretion in INS-1E \u03b2-Cells"],"prefix":"10.1055","volume":"120","author":[{"given":"A.","family":"Natali","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Department of Internal Medicine, University of Pisa, Italy and Chronic Diseases Research Centre, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Portugal"}]},{"given":"E.","family":"Santini","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Department of Internal Medicine, University of Pisa, Italy"}]},{"given":"A.","family":"Delbarba","sequence":"additional","affiliation":[{"name":"Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milano"}]},{"given":"S.","family":"Baldi","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Department of Internal Medicine, University of Pisa, Italy"}]},{"given":"E.","family":"Venturi","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Department of Internal Medicine, University of Pisa, Italy"}]},{"given":"A.","family":"Tulipani","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Department of Internal Medicine, University of Pisa, Italy"}]},{"given":"E.","family":"Nisoli","sequence":"additional","affiliation":[{"name":"Center for Study and Research on Obesity, Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milano"}]},{"given":"E.","family":"Ferrannini","sequence":"additional","affiliation":[{"name":"Metabolism Unit, Department of Internal Medicine, University of Pisa, Italy"}]}],"member":"194","published-online":{"date-parts":[[2012,2,10]]},"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0031-1298015.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T14:44:12Z","timestamp":1691160252000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0031-1298015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,10]]},"references-count":0,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2012,4,23]]},"published-print":{"date-parts":[[2012,4]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0031-1298015","relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,10]]}}}