Decrease of Serum Ascorbic Acid Concentrations in Patients with Diabetic Macroangiopathy.

Nagano, Seishi; Kurokawa, Munekazu; Ebara, Tetsu; Naito, Hirokuni; Sakamaki, Ryoichi; Furukawa, Seiichi; Hirano, Tsutomu; Maeda, Masako; Tsuji, Akio

doi:10.3177/jnsv.42.1

Cited by 6 publications

(2 citation statements)

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“…Ineffective recruitment of GLUT4 to the cell surface results in excessive glucose accumulation in the blood and type II diabetes clinically. In addition to aberrant glucose metabolism, some evidence suggests that diabetics may also have decreased cellular concentrations of ascorbate or increased requirements for it (14)(15)(16)(17). Considering the importance of GLUT4 in glucose uptake and its possible implications in ascorbate metabolism, it was worthwhile to pursue investigation of DHA transport by GLUT4.…”

Section: Introductionmentioning

confidence: 99%

Dehydroascorbic Acid Transport by GLUT4 in XenopusOocytes and Isolated Rat Adipocytes

Rumsey¹,

Daruwala²,

Al-Hasani³

et al. 2000

Journal of Biological Chemistry

184

125

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Dehydroascorbic acid (DHA), the first stable oxidation product of vitamin C, was transported by GLUT1 and GLUT3 in Xenopus laevis oocytes with transport rates similar to that of 2-deoxyglucose (2-DG), but due to inherent difficulties with GLUT4 expression in oocytes it was uncertain whether GLUT4 transported DHA (Rumsey, S. C. , Kwon, O., Xu, G. W., Burant, C. F., Simpson, I., and Levine, M. (1997) J. Biol. Chem. 272, 18982-18989). We therefore studied DHA and 2-DG transport in rat adipocytes, which express GLUT4. Without insulin, rat adipocytes transported 2-DG 2-3-fold faster than DHA. Preincubation with insulin (0.67 micrometer) increased transport of each substrate similarly: 7-10-fold for 2-DG and 6-8-fold for DHA. Because intracellular reduction of DHA in adipocytes was complete before and after insulin stimulation, increased transport of DHA was not explained by increased internal reduction of DHA to ascorbate. To determine apparent transport kinetics of GLUT4 for DHA, GLUT4 expression in Xenopus oocytes was reexamined. Preincubation of oocytes for >4 h with insulin (1 micrometer) augmented GLUT4 transport of 2-DG and DHA by up to 5-fold. Transport of both substrates was inhibited by cytochalasin B and displayed saturable kinetics. GLUT4 had a higher apparent transport affinity (K(m) of 0.98 versus 5.2 mm) and lower maximal transport rate (V(max) of 66 versus 880 pmol/oocyte/10 min) for DHA compared with 2-DG. The lower transport rate for DHA could not be explained by binding differences at the outer membrane face, as shown by inhibition with ethylidene glucose, or by transporter trans-activation and therefore was probably due to substrate-specific differences in transporter/substrate translocation or release. These novel data indicate that the insulin-sensitive transporter GLUT4 transports DHA in both rat adipocytes and Xenopus oocytes. Alterations of this mechanism in diabetes could have clinical implications for ascorbate utilization.

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