title: Hyperoxia inhibits glucose-induced insulin secretion and mitochondrial metabolism in rat pancreatic islets.
abstract: Isolated pancreatic islets containing the insulin-producing beta cells are devoid of circulation. They may therefore experience hypoxia with possible negative effects on beta cell function and survival. We investigated (1) whether hyperoxia in vitro would be beneficial by counteracting putative effects of lost circulation and, further, (2) whether previous hyperoxia would attenuate the impact of subsequently induced severe hypoxia. Islets from Sprague-Dawley rats were exposed to 95% O2 for 18 h. This hyperoxic exposure diminished glucose-induced insulin secretion by 47% and inhibited oxygen consumption by 39-41%. Mitochondrial complexes I-III were decreased by 29-37%. Negative effects on insulin secretion and complexes III and IV waned after a 22 h period of normoxia following hyperoxia whereas complexes I and II were still diminished, ROS production was increased and rates of apoptosis tended to be increased (P=0.07). The effects of previous hyperoxia on susceptibility to damage by subsequent hypoxia were tested after 5.5h of 0.8% O2. Previous hyperoxia did not affect hypoxia-induced enhancement of HIF-1 alpha but modestly and significantly attenuated hypoxia-induced decreases in insulin contents. We conclude that hyperoxia exerts largely negative effects on beta cells, effects which are functional and possibly also toxic. A paradoxical positive finding (attenuation of hypoxia-induced effects) could be secondary to a protective effect of the hyperoxia-induced reduction of oxidative metabolism.
authors.affiliation: Dept. of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors.forename: Zuheng
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Dept. of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors.forename: Noah
authors.initials: N
authors.lastname: Moruzzi
authors.affiliation: Dept. of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden.
authors.forename: Sergiu-Bogdan
authors.initials: SB
authors.lastname: Catrina
authors.affiliation: Dept. of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden; Institute of Cancer Research and Molecular Medicine, The Medical Faculty, Norwegian University of Science and Technology, 7006 Trondheim, Norway; Dept. of Endocrinology, St. Olav University Hospital, 7006 Trondheim, Norway.
authors.forename: Valdemar
authors.initials: V
authors.lastname: Grill
authors.affiliation: Dept. of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden. Electronic address: anneli.bjorklund@ki.se.
authors.forename: Anneli
authors.initials: A
authors.lastname: Björklund
mesh_terms: D000818:Animals; D017209:Apoptosis; D002469:Cell Separation; D004247:DNA / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D017382:Reactive Oxygen Species; D004247:DNA; D005947:Glucose; D010100:Oxygen
keywords: Hyperoxia; Insulin biosynthesis; Insulin secretion