TITLE:
Insulin Release from the Beta Cells in Acatalasemic Mice Is Highly Susceptible to Alloxan-Induced Oxidative Stress
AUTHORS:
Kazunori Takemoto, Wakana Doi, Ken Kataoka, Kohji Ishihara, Da-Hong Wang, Hitoshi Sugiyama, Noriyoshi Masuoka
KEYWORDS:
Alloxan, Hyperglycemia, Acatalasemia, Insulin Release, Diabetes, Beta Cells
JOURNAL NAME:
Journal of Diabetes Mellitus,
Vol.5 No.2,
May
5,
2015
ABSTRACT: Background: Catalase deficiency
(acatalasemia) is sensitive to alloxan, and the administration to acatalasemic
mice develops hyperglycemia under mild conditions. However, the mechanism is
still poorly understood. Methods: Alloxan was used to induce the oxidative
stress and intraperitoneally administered to acatalasemic and normal mice. The
blood samples of these mice after 1, 3, 5 and 7 days were examined. The
pancreatic islets 7 days after alloxan administration were isolated, and the
insulin released under 3 mM and 20 mM glucose was examined. Results: After
alloxan administration, increase of oxidative markers in blood and pancreatic
apoptosis in acatalasemic mice were observed immediately. Insulin in blood was
lowered after 3 days, and the insulin in acatalasemic mice was lower than that
in normal mice. Hyperglycemia in the acatalasemic mice was observed after 3
days. The pancreatic islets after 7 days were isolated. A reduction of the
insulin released from the islets under glucose stimulation was observed. The
stimulation indexes of the normal and acatalasemic mice were 1.4 ± 0.6 and 0.7
± 0.3, respectively. Conclusions: Alloxan induced a deterioration of
glucose-dependent insulin secretion ability from the islets, and the
deterioration mostly contributed to hyperglycemia, rather than apoptosis.