Abnormal myoinositol influx in human leucocytes in diabetes but not specifically in diabetic neuropathy.
Abnormal myoinositol metabolism has been implicated as a contributor to the development of diabetic neuropathy. Furthermore, in vitro glucose inhibits animal and human myoinositol transporters. To investigate whether myoinositol transport is abnormal in diabetic subjects with and without neuropathy, we used a triple-isotope technique to measure [14C]myoinositol uptake in leucocytes from 23 insulin-dependent diabetic subjects and 13 matched nondiabetic subjects. All subjects with diabetes underwent neurophysiological studies, and subjects without neuropathy were compared with those with various degrees of neuropathy. The relationship between glycemia and flux was also studied. Diabetic subjects had similar intracellular and plasma myoinositol concentrations but had higher rates of uptake of myoinositol over the extracellular concentrations of myoinositol studied. Although the derived Km, Vmax, and passive components were not significantly different, the Vmax:Km ratio was significantly higher in diabetic subjects compared with nondiabetic subjects (0.25 [0.17-0.32] vs. 0.16 [0.13-0.19], respectively (P = 0.006). In diabetic subjects, the rate of myoinositol uptake correlated with HbA1c, particularly at 3 microM extracellular myoinositol where active uptake was a high proportion of the total influx (P less than 0.005). No difference in myoinositol uptake was found among diabetic subjects with various degrees of neuropathy. We conclude that although myoinositol transport is abnormal in diabetes, it is not specifically abnormal in diabetic neuropathy. Prolonged hyperglycemia is associated with higher myoinositol flux.
Simmons
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Sheikh Rashid Diabetes Unit, Radcliffe Infirmary, Oxford, UK.
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Bomford
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D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002250:Carbon Radioisotopes; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D007294:Inositol / Q000097:blood*; D007700:Kinetics; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction; D010525:Peripheral Nerves / Q000503:physiopathology; D012016:Reference Values; D014316:Tritium
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D006442:Glycated Hemoglobin; D007294:Inositol; D014316:Tritium