title: Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.
abstract: Human acatalasemia may be a risk factor for the development of diabetes mellitus. However, the mechanism by which diabetes is induced is still poorly understood. The impact of catalase deficiency on the onset of diabetes has been studied in homozygous acatalasemic mutant mice or control wild-type mice by intraperitoneal injection of diabetogenic alloxan. The incidence of diabetes was higher in acatalasemic mice treated with a high dose (180 mg/kg body weight) of alloxan. A higher dose of alloxan accelerated severe atrophy of pancreatic islets and induced pancreatic beta cell apoptosis in acatalasemic mice in comparison to wild-type mice. Catalase activity remained low in the acatalasemic pancreas without the significant compensatory up-regulation of glutathione peroxidase or superoxide dismutase. Furthermore, daily intraperitoneal injection of angiotensin II type 1 (AT1) receptor antagonist telmisartan (0.1 mg/kg body weight) prevented the development of alloxan-induced hyperglycemia in acatalasemic mice. This study suggests that catalase plays a crucial role in the defense against oxidative-stress-mediated pancreatic beta cell death in an alloxan-induced diabetes mouse model. Treatment with telmisartan may prevent the onset of alloxan-induced diabetes even under acatalasemic conditions.
authors.affiliation: Department of Medicine and Clinical Science, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kikumoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morinaga
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takiue
authors.forename: Masashi
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Fukuoka
authors.forename: Mizuho
authors.initials: M
authors.lastname: Saeki
authors.forename: Yohei
authors.initials: Y
authors.lastname: Maeshima
authors.forename: Da-Hong
authors.initials: DH
authors.lastname: Wang
authors.forename: Keiki
authors.initials: K
authors.lastname: Ogino
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Masuoka
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D020642:Acatalasia / Q000378:metabolism; D000496:Alloxan; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles / Q000627:therapeutic use; D001565:Benzoates / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D016923:Cell Death; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D005979:Glutathione Peroxidase / Q000378:metabolism; D006720:Homozygote; D006943:Hyperglycemia / Q000201:enzymology / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000502:physiology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D000077333:Telmisartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D001786:Blood Glucose; D000496:Alloxan; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000077333:Telmisartan