Effect of streptozotocin-induced diabetes on rat liver Na+/K+-ATPase.
Na+/K+-ATPase during diabetes may be regulated by synthesis of its alpha and beta subunits and by changes in membrane fluidity and lipid composition. As these mechanisms were unknown in liver, we studied in rats the effect of streptozotocin-induced diabetes on liver Na+/K+-ATPase. We then evaluated whether fish oil treatment prevented the diabetes-induced changes. Diabetes mellitus induced an increased Na+/K+-ATPase activity and an enhanced expression of the beta1 subunit; there was no change in the amount of the alpha1 and beta3 isoenzymes. Biphasic ouabain inhibition curves were obtained for diabetic groups indicating the presence of low and high affinity sites. No alpha2 and alpha3 isoenzymes could be detected. Diabetes mellitus led to a decrease in membrane fluidity and a change in membrane lipid composition. The diabetes-induced changes are not prevented by fish oil treatment. The results suggest that the increase of Na+/K+-ATPase activity can be associated with the enhanced expression of the beta1 subunit in the diabetic state, but cannot be attributed to changes in membrane fluidity as typically this enzyme will increase in response to an enhancement of membrane fluidity. The presence of a high-affinity site for ouabain (IC50 = 10-7 M) could be explained by the presence of (alphabeta)2 diprotomeric structure of Na+/K+-ATPase or an as yet unknown alpha subunit isoform that may exist in diabetes mellitus. These stimulations might be related, in part, to the modification of fatty acid content during diabetes.
Sennoune
S
S
Laboratoire de Recherche Cardiologique, Faculté de Medecine Nord, Marseille, France.
Gerbi
A
A
Duran
M J
MJ
Grillasca
J P
JP
Compe
E
E
Pierre
S
S
Planells
R
R
Bourdeaux
M
M
Vague
P
P
Pieroni
G
G
Maixent
J M
JM
D000818:Animals; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D017931:DNA Primers; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013311:Streptozocin
D001786:Blood Glucose; D017931:DNA Primers; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D007527:Isoenzymes; D008563:Membrane Lipids; D010042:Ouabain; D013311:Streptozocin; D000254:Sodium-Potassium-Exchanging ATPase