Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice

Yoko Kikumoto (1) , Hitoshi Sugiyama (1, 2) , Tatsuyuki Inoue (1) , Hiroshi Morinaga (1) , Keiichi Takiue (1) , Masashi Kitagawa (1) , Naomi Fukuoka (1) , Mizuho Saeki (1) , Yohei Maeshima (1) , Da-Hong Wang , Keiki Ogino , Noriyoshi Masuoka (3) , Hirofumi Makino (1)

1 Department of Medicine and Clinical Science
2 Okayama University Graduate School of Medicine
3 Department of Life Science

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 β 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 (0.1mg/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 β cell death in an alloxan-induced diabetes mouse model. Treatment with telmisartan may prevent the onset of alloxan-induced diabetes even under acatalasemic conditions.

Mots clés: Acatalasemia; Diabetes mellitus; Oxidative stress; Catalase; Apoptosis; Angiotensin receptor antagonist

Yoko Kikumoto, Hitoshi Sugiyama, Tatsuyuki Inoue, Hiroshi Morinaga, Keiichi Takiue, et al.. Sensitization to alloxan-induced diabetes and pancreatic cell apoptosis in acatalasemic mice. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010, ⟨10.1016/j.bbadis.2009.10.009⟩. ⟨hal-00562945⟩