{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T15:27:27Z","timestamp":1772897247457,"version":"3.50.1"},"reference-count":0,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1997,8,1]]},"abstract":"<jats:p> Recent observations suggest that carbon monoxide (CO) may serve as a neuroendocrine modulator in hypothalamus. Here we provide evidence, for the first time, that the islets of Langerhans contain the constitutive isoform of the CO-producing enzyme heme oxygenase (HO-2), the activity of which was found to modulate islet hormone release. Most insulin and glucagon cells in the rat endocrine pancreas expressed strong immunoreactivity for HO-2. In the exocrine parenchyma, scattered HO-2-positive ganglionic cell bodies were occasionally observed. Furthermore, Western blot analysis revealed the presence of HO-2 in isolated islets but not in acinar cells. Islet homogenates displayed a comparatively high HO-2 enzymatic activity measured as CO formation (approximately 600 pmol CO.min-1.mg islet protein-1). This HO-2 enzymatic activity was greatly suppressed by zincprotoporphyrin-IX (ZnPP-IX), a recognized inhibitor of HO activity. Neither ZnPP-IX nor the HO activator, hemin, influenced basal insulin release from isolated rat islets at low (1 mM) glucose. However, glucagon release at 1 mM glucose was increased by hemin and inhibited by ZnPP-IX. The hemin-induced increase in glucagon secretion was abolished by ZnPP-IX. Furthermore, a series of experiments at high glucose (16.7 mM) revealed that hemin induced a dose-dependent potentiation of glucose-stimulated insulin release. Moreover, glucose-induced insulin release was dose-dependently suppressed by ZnPP-IX but unaffected by protoporphyrin-IX, a compound known not to influence HO-2 activity in other tissues. Similarly, glucagon release at high glucose was dose-dependently increased by hemin and suppressed by ZnPP-IX. Finally, the hemin-induced increase in islet hormone release at high glucose was totally abolished by ZnPP-IX. The data strongly suggest that CO production positively modulates both glucagon and insulin secretion. We propose that CO may serve as a novel messenger molecule within the islets of Langerhans. <\/jats:p>","DOI":"10.1152\/ajpcell.1997.273.2.c703","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T16:07:55Z","timestamp":1514131675000},"page":"C703-C709","source":"Crossref","is-referenced-by-count":31,"title":["Occurrence and putative hormone regulatory function of a constitutive heme oxygenase in rat pancreatic islets"],"prefix":"10.1152","volume":"273","author":[{"given":"R.","family":"Henningsson","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Lund, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Alm","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Lund, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Lundquist","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Lund, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.1997.273.2.C703","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:32:12Z","timestamp":1718652732000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.1997.273.2.C703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,8,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1997,8,1]]}},"alternative-id":["10.1152\/ajpcell.1997.273.2.C703"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.1997.273.2.c703","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,8,1]]}}}