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

Autor: Mizuho Saeki, Noriyoshi Masuoka, Hiroshi Morinaga, Yohei Maeshima, Yoko Kikumoto, Masashi Kitagawa, Naomi Fukuoka, Keiichi Takiue, Keiki Ogino, Hirofumi Makino, Hitoshi Sugiyama, Tatsuyuki Inoue, Da Hong Wang
Přispěvatelé: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Department of Life Science, Okayama University
Rok vydání: 2010
Předmět:
Blood Glucose
Male
endocrine system diseases
medicine.medical_treatment
Apoptosis
Benzoates
Mice
chemistry.chemical_compound
0302 clinical medicine
Diabetes mellitus
Insulin-Secreting Cells
Alloxan
Telmisartan
Mice
Knockout
chemistry.chemical_classification
Mice
Inbred C3H
0303 health sciences
Cell Death
Glutathione peroxidase
Angiotensin II
Homozygote
Receptor antagonist
Catalase
3. Good health
medicine.anatomical_structure
030220 oncology & carcinogenesis
Angiotensin receptor antagonist
Molecular Medicine
Pancreas
medicine.drug
medicine.medical_specialty
Intraperitoneal injection
Diabetes Mellitus
Experimental
Acatalasia
03 medical and health sciences
Internal medicine
medicine
Animals
Molecular Biology
030304 developmental biology
Glutathione Peroxidase
Superoxide Dismutase
Pancreatic islets
Body Weight
Acatalasemia
medicine.disease
Mice
Mutant Strains
Endocrinology
chemistry
Oxidative stress
Hyperglycemia
Benzimidazoles
Angiotensin II Type 1 Receptor Blockers
Zdroj: Biochimica et Biophysica Acta-Molecular Basis of Disease
Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2010, ⟨10.1016/j.bbadis.2009.10.009⟩
ISSN: 0925-4439
DOI: 10.1016/j.bbadis.2009.10.009
Popis: International audience; 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.
Databáze: OpenAIRE
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