Na(+)-K(+)-ATPase and changes in ATP hydrolysis, monovalent cation affinity, and K+ occlusion in diabetic and galactosemic rats.
This study showed that steady-state kinetics of ATP hydrolysis by Na(+)-K(+)-ATPase are altered in the BB Wistar diabetic rat and experimental galactosemia. Four days after onset, this change was not evident if NaCNBH3 was omitted during enzyme preparations (indicating reversibility). Ninety days after onset, NaCNBH3 reduction was not necessary to see the change in ATP hydrolysis kinetics (indicating nonreversibility). The change in steady-state ATP hydrolysis was similar to that reported earlier for Na(+)-K(+)-ATPase of the lens epithelium and kidney medulla of diabetic individuals and for two in vitro glycosylation models. Our study also showed that the affinities of Na(+)-K(+)-ATPase for K+ are altered, and Na(+)-K(+)-ATPase-dependent K+ occlusion is inhibited in diabetic and galactosemic animals. Because K+ occlusion is required for efficient K+ transport, this finding supports previous in vitro studies that indicated that glycosylation inhibits pump-dependent K+ transport. Furthermore, our study suggested an irreversible impairment of Na(+)-K(+)-ATPase function in the diabetic BB Wistar rat as early as 15 days after onset, even when blood glucose was maintained at 6.7 mM by daily insulin injection.
Tehrani
S T
ST
Department of Ophthalmology, California College of Medicine, University of California, Irvine 92717.
Yamamoto
J J
JJ
Garner
M H
MH
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002414:Cations, Monovalent / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004848:Epithelium / Q000201:enzymology / Q000503:physiopathology; D005693:Galactosemias / Q000378:metabolism* / Q000503:physiopathology; D006868:Hydrolysis; D007679:Kidney Medulla / Q000201:enzymology / Q000503:physiopathology; D007908:Lens, Crystalline / Q000201:enzymology / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism* / Q000502:physiology
D002414:Cations, Monovalent; D000255:Adenosine Triphosphate; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium