title: Cellular hypoxia of pancreatic beta-cells due to high levels of oxygen consumption for insulin secretion in vitro.
abstract: Cellular oxygen consumption is a determinant of intracellular oxygen levels. Because of the high demand of mitochondrial respiration during insulin secretion, pancreatic β-cells consume large amounts of oxygen in a short time period. We examined the effect of insulin secretion on cellular oxygen tension in vitro. We confirmed that Western blotting of pimonidazole adduct was more sensitive than immunostaining for detection of cellular hypoxia in vitro and in vivo. The islets of the diabetic mice but not those of normal mice were hypoxic, especially when a high dose of glucose was loaded. In MIN6 cells, a pancreatic β-cell line, pimonidazole adduct formation and stabilization of hypoxia-inducible factor-1α (HIF-1α) were detected under mildly hypoxic conditions. Inhibition of respiration rescued the cells from becoming hypoxic. Glucose stimulation decreased cellular oxygen levels in parallel with increased insulin secretion and mitochondrial respiration. The cellular hypoxia by glucose stimulation was also observed in the isolated islets from mice. The MIN6 cells overexpressing HIF-1α were resistant to becoming hypoxic after glucose stimulation. Thus, glucose-stimulated β-cells can become hypoxic by oxygen consumption, especially when the oxygen supply is impaired.
authors.affiliation: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-8511.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Hiroko
authors.initials: H
authors.lastname: Endo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okuyama
authors.forename: Takaaki
authors.initials: T
authors.lastname: Takeda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yamagata
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010101:Oxygen Consumption / Q000502:physiology*
chemical_list: D007328:Insulin