Effect of Ascorbate and Dehydroascorbate on Tissue Uptake of Glucose

In vitro studies have suggested that ascorbate or dehydroascorbate share with glucose the same tissue-transport carrier. To determine if ascorbic acid or its oxidized form can inhibit tissue uptake of glucose, the brain uptake index (BUI) and muscle uptake index of glucose were determined by single arterial injection tissue-sampling technique. The injectate was either buffered Ringer's solution with varying concentrations of ascorbate, dehydroascorbate (pH 7.4), or 70% serum from individuals on vitamin C supplements. Ascorbic acid over a wide range of concentrations (0–10,000 mg/L) did not reduce the BUI. Ascorbic acid reduced BUI from the control value of 33 ± 3.2 to 20.1 ± 2.2% (P < .01) only at 100,000 mg/L; this effect was probably secondary to osmotic disruption of blood-brain barrier. In contrast, dehydroascorbate inhibited the BUI of glucose from baseline value of 32.8 ± 1.1 to 10.7 ± 0.67%, with an estimated K, of 13.0 mM. Masseter muscle glucose uptake was not significantly altered over a wide range of ascorbate or dehydroascorbate concentrations in the injectate. Dehydroascorbate (7500 mg/L) did not significantly reduce the BUI of [¹⁴C]phenylalanine (55.2 ± 4.4 vs. 62.1 ± 4.2% in controls). When serum from six individuals on calcium ascorbate (3–5 g/day) was compared with that of nine controls, the BUI was not different (19.3 ± 1.7 vs. 19.3 ± 1.1%). Similarly, supplementing the diet of eight healthy volunteers with 1 g calcium ascorbate for 8 days did not alter the BUI of glucose. We conclude that dehydroascorbic acid, but not ascorbic acid, inhibits in vivo brain but not muscle uptake of glucose, suggesting a common carrier system at the level of the blood-brain barrier. The low serum levels of ascorbate even after vitamin C supplementation are not sufficient to impair brain glucose uptake.