Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice.
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.
Kikumoto
Yoko
Y
Department of Medicine and Clinical Science, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Sugiyama
Hitoshi
H
Inoue
Tatsuyuki
T
Morinaga
Hiroshi
H
Takiue
Keiichi
K
Kitagawa
Masashi
M
Fukuoka
Naomi
N
Saeki
Mizuho
M
Maeshima
Yohei
Y
Wang
Da-Hong
DH
Ogino
Keiki
K
Masuoka
Noriyoshi
N
Makino
Hirofumi
H
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
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