Comparison of Ascorbic Acid Levels and Hepatic L-Gulonolactone Oxidase Activity in KK-Ay Mice and Streptozotocin-Diabetic Mice under Hyperglycemic Conditions.

Abstract

Blood ascorbic acid (AsA) concentrations are lower in diabetic patients than in the general population, a phenomenon that is also observed in streptozotocin (STZ)-diabetic models of type 1 diabetes. However, the occurrence of diabetes in KK-Ay mice, a model for type 2 diabetes, the most common form of diabetes, remains unclear. Although this mouse can synthesize AsA, understanding its level changes during diabetes progression could help in analyzing AsA's effects on type 2 diabetes. Therefore, the present study investigated the relationship between hyperglycemia and AsA concentrations in the blood and organs of KK-Ay mice, and discussed the findings in relation to those observed in STZ-diabetic mice. Male KK-Ay mice were examined at different stages of diabetes (pre-diabetic, early onset, and hyperglycemic maintenance). STZ-diabetic mice were generated by administering STZ to ICR mice. AsA concentrations were measured in plasma, blood mononuclear cells, and tissues, along with hepatic L-gulonolactone oxidase (GLO) activity and mRNA expression levels. Unexpectedly, AsA concentrations in KK-Ay mice increased under hyperglycemic conditions, while they decreased in STZ-diabetic mice. A consistent relationship was not observed between organ AsA concentrations and hyperglycemia. GLO activity and mRNA expression levels increased in KK-Ay mice, but decreased in STZ-diabetic mice, suggesting an innate defense mechanism against hyperglycemia in KK-Ay mice. These results indicate that different diabetes models exhibit distinct changes in AsA concentrations and hepatic GLO activity under hyperglycemic conditions, highlighting the importance of considering endogenous AsA when evaluating the antioxidant properties of dietary components in KK-Ay mice.