Attenuation of both the active transport of myo-inositol and Na+-K+-ATPase pumping activity has been implicated in the onset of sugar cataract and other diabetic complications in cell culture and animal models of the disease. Cultured bovine lens epithelial cells (BLECs) maintained in galactose-free Eagle's minimal essential medium (MEM) or 40 mM galactose with and without sorbinil for up to 5 days were examined to determine the temporal effects of hypergalactosemia on Na+-K+-ATPase and myo-inositol uptake. The Na+-K+-ATPase pumping activity after 5 days of continuous exposure to galactose did not change, as demonstrated by 86Rb uptake. The uptake of myo-[3H]inositol was lowered after 20 h of incubation in galactose and remained significantly below that of the control throughout the 5-day exposure period. The coadministration of sorbinil to the galactose medium normalized the myo-[3H]inositol uptake. No significant difference in the rates of passive efflux of myo-[3H]inositol or 86Rb from preloaded galactose-treated and control cultures was observed. Culture-media reversal studies were also carried out to determine whether the galactose-induced dysfunction in myo-inositol uptake could be corrected. BLECs were incubated in galactose for 5 days, then changed to galactose-free physiological medium with and without sorbinil for a 1-day recovery period. myo-Inositol uptake was reduced to 34% of control after 6 days of continuous exposure to galactose. Within 24 h of media reversal, myo-inositol uptake returned to or exceeded control values in BLECs switched to either MEM or MEM with sorbinil. These observations support the contention that the aldose reductase reaction or formation of the product of the aldose reductase reaction disrupted lens cell myo-inositol uptake. Although the coadministration of sorbinil to the galactose medium protected against the attendant decrease in transport activity, the cessation of exposure of BLECs to galactose was sufficient stimulus to normalize myo-inositol uptake. Moreover, these observations suggested that the deficit in myoinositol uptake elicited by exposure to galactose was reversible and occurred independently of changes in Na+-K+-ATPase pumping activity in cultured lens epithelium, indicating that the two parameters are not strictly associated and that the deficit in myo-inositol uptake occurs rapidly during hypergalactosemia.
Uncoupling of Attenuated myo-[3H]Inositol Uptake and Dysfunction in Na+-K+-ATPase Pumping Activity in Hypergalactosemic Cultured Bovine Lens Epithelial Cells
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Patrick R Cammarata, Daniel Tse, Thomas Yorio; Uncoupling of Attenuated myo-[3H]Inositol Uptake and Dysfunction in Na+-K+-ATPase Pumping Activity in Hypergalactosemic Cultured Bovine Lens Epithelial Cells. Diabetes 1 June 1991; 40 (6): 731–737. https://doi.org/10.2337/diab.40.6.731
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