title: Culture at low glucose up-regulates mitochondrial function in pancreatic β cells with accompanying effects on viability.
abstract: We tested whether exposure of β cells at reduced glucose leads to mitochondrial adaptions and whether such adaptions modulate effects of hypoxia. Rat islets, human islets and INS-1 832/13 cells were pre-cultured short term at half standard glucose concentrations (5.5 mM for rat islets and cells, 2.75 mM for human islets) without overtly negative effects on subsequently measured function (insulin secretion and cellular insulin contents) or on viability. Culture at half standard glucose upregulated complex I and tended to upregulate complex II in islets and INS-1 cells alike. An increased release of lactate dehydrogenase that followed exposure to hypoxia was attenuated in rat islets which had been pre-cultured at half standard glucose. In INS-1 cells exposure to half standard glucose attenuated hypoxia-induced effects on several viability parameters (MTT, cell number and incremental apoptotic DNA). Thus culture at reduced glucose of pancreatic islets and clonal β cells leads to mitochondrial adaptions which possibly lessen the negative impact of hypoxia on β cell viability. These findings appear relevant in the search for optimization of pre-transplant conditions in a clinical setting.
authors.affiliation: a Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology (NTNU) , Trondheim , Norway.|d Department of Endocrinology , St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway.
authors.forename: Ingrid K
authors.initials: IK
authors.lastname: Hals
authors.affiliation: a Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology (NTNU) , Trondheim , Norway.
authors.forename: Rinku
authors.initials: R
authors.lastname: Singh
authors.affiliation: b Department of Molecular Medicine and Surgery , Karolinska Institutet , Stockholm , Sweden.
authors.forename: Zuheng
authors.initials: Z
authors.lastname: Ma
authors.affiliation: c Department of Transplantation Medicine and Institute for Surgical Research , Oslo University Hospital , Oslo , Norway.
authors.forename: Hanne
authors.initials: H
authors.lastname: Scholz
authors.affiliation: b Department of Molecular Medicine and Surgery , Karolinska Institutet , Stockholm , Sweden.
authors.forename: Anneli
authors.initials: A
authors.lastname: Björklund
authors.affiliation: a Department of Cancer Research and Molecular Medicine , Norwegian University of Science and Technology (NTNU) , Trondheim , Norway.|d Department of Endocrinology , St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway.
authors.forename: Valdemar
authors.initials: V
authors.lastname: Grill
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051381:Rats
chemical_list: D005947:Glucose
keywords: INS-1; hypoxia; insulin secretion; low glucose; mitochondrial complexes; oxygen consumption; rat and human islets; viability