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.
Highlights
Catalase (EC1.11.1.6) plays a predominant role in the removal of hydrogen peroxide that is necessary to afford protection against the oxidative damage caused by high concentrations of hydrogen peroxide [1]
To make clear the reason why the high incidence of diabetes in acatalasemia patients was observed, we have examined acatalasemic mice established by Feinstein et al [5] and normal mice by intrapenitoneal injection of diabetogenic alloxan [6]-[9]
We examined insulin release from the Langerhans islets isolated from alloxan-treated mice under glucose stimulation to investigate what kind of oxidative damage occurs in the pancreas, since it is widely accepted that diabetes is associated with reactive oxygen species, which contribute to pancreatic cell damage and dysfunction in both type 1 and type 2 diabetes [12]
Summary
Catalase (EC1.11.1.6) plays a predominant role in the removal of hydrogen peroxide that is necessary to afford protection against the oxidative damage caused by high concentrations of hydrogen peroxide [1]. To make clear the reason why the high incidence of diabetes in acatalasemia patients was observed, we have examined acatalasemic mice established by Feinstein et al [5] and normal mice by intrapenitoneal injection of diabetogenic alloxan [6]-[9]. Increase of apoptosis in Langerhans islets was observed in acatalasemic mice but in normal mice. 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. Conclusions: Alloxan induced a deterioration of glucose-dependent insulin secretion ability from the islets, and the deterioration mostly contributed to hyperglycemia, rather than apoptosis
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