Aberrant vitamin C physiology in diabetes: a mouse model

Authors

• SE Levitt
• MA Levine
• K Patra

Abstract

Compared to healthy people, people with diabetes have lower plasma Vitamin C (ascorbate) concentrations, but reasons for this are uncertain. To understand why, we developed a mouse model of diabetes using mice unable to make vitamin C: gulonolactone-oxidase knockout mice (gulo-/-) treated with steptozotocin to induce insulin-deficient diabetes. Similar to humans, gulo-/- mice had a vitamin C renal threshold of approximately 60uM. Diabetes induced left shifting of the renal threshold, a renal leak, so that the renal threshold in diabetic gulo-/- mice was approximately 41uM. When plasma vitamin C concentrations were below the renal threshold in both non-diabetic and diabetic gulo-/- mice, so that there was no renal loss, plasma vitamin C decay rate was faster in diabetic compared to healthy mice: 1.3 ± 0.16 µg /hr vs. 0.31 ± 0.06 µg /hr (p<0.001). One explanation of decay rate differences is decreased reduction of dehydroascorbic acid (oxidized ascorbate) in diabetic red blood cells compared to controls. However, dehydroascorbic acid reduction was similar in both. Other explanations of decay rate differences are: decreased transmembrane electron transfer from internal red cell ascorbate to ascorbate radical in plasma; competition of dehydroascorbic acid into RBCs by glucose; or increased utilization of vitamin C in diabetes independent of red blood cells. Experiments to test these possibilities are underway. The findings show that a mouse model can aid in probing multiple aberrancies of vitamin C physiology in diabetes.

Scientific Focus Area: Molecular Biology and Biochemistry

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