title: Cytosolic O-GlcNAc accumulation is not involved in beta-cell death in HIT-T15 or Min6.
abstract: O-linked N-acetylglucosamine (O-GlcNAc) is attached to and detached from proteins by O-GlcNAc transferase (OGT) and O-GlcNAcase, respectively. It has been proposed that streptozotocin induces pancreatic beta-cell death by blocking O-GlcNAcase and increasing O-GlcNAc. To elucidate the relationship between cytosolic O-GlcNAc accumulation and beta-cell death, we treated beta-cell lines HIT-T15 and Min6 with glucosamine. Glucosamine markedly reduced cell viability in both cell lines only at 10 mM. The measurement of cytosolic O-GlcNAc under glucosamine treatment revealed that O-GlcNAc accumulation was observed even at 2 mM glucosamine and maximized at 5 mM, but did not occur very well at 10 mM. Furthermore, 100 microM PUGNAc, an inhibitor of O-GlcNAcase, increased cytosolic O-GlcNAc but did not induce cell death in these cells. Therefore, no correlation between accumulation of cytosolic O-GlcNAc and beta-cell death was suggested. Alternatively, inosine partially rescued cell death induced by glucosamine in Min6 cells, suggesting that energy depletion partly contributes to beta-cell death by glucosamine.
authors.affiliation: Pharmacology and Molecular Biology Research Laboratories, Sankyo Co. Ltd., 2-58 Hiromachi-1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. ryooku@shina.sankyo.co.jp
authors.forename: R
authors.initials: R
authors.lastname: Okuyama
authors.forename: M
authors.initials: M
authors.lastname: Yachi
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000118:Acetylglucosaminidase / Q000037:antagonists & inhibitors; D000818:Animals; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005944:Glucosamine / Q000494:pharmacology; D051548:Histone Acetyltransferases; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009097:Multienzyme Complexes; D010091:Oximes / Q000494:pharmacology; D048448:Phenylcarbamates; D001619:beta-N-Acetylhexosaminidases
chemical_list: D009097:Multienzyme Complexes; D010091:Oximes; D048448:Phenylcarbamates; C068836:N-acetylglucosaminono-1,5-lactone O-(phenylcarbamoyl)oxime; D051548:Histone Acetyltransferases; C110628:hexosaminidase C; D000118:Acetylglucosaminidase; D001619:beta-N-Acetylhexosaminidases; D005944:Glucosamine; D000117:Acetylglucosamine