Mechanism of increased tubular Na-K-ATPase during streptozotocin-induced diabetes.
Since the mechanisms responsible for stimulation of kidney Na-K-ATPase during streptozotocin-induced diabetes are unknown, we studied the possible role(s) of kidney hyperfiltration and hypertrophy and of hyperaldosteronism on Na-K-ATPase induction. For this purpose, we studied the relationship between Na-K-ATPase activity in individual nephron segments and alterations of glomerular filtration rate during the early phase of diabetes. Within 2 days after streptozotocin administration, Na-K-ATPase activity markedly increased in the proximal convoluted tubule, medullary thick ascending limb and cortical and outer medullary collecting tubule, but not in the proximal straight tubule, cortical thick ascending limb and distal convoluted tubule. Streptozotocin administration also markedly enhanced the glomerular filtration rate but only after 4 days following initiation of treatment. Changes in Na-K-ATPase were specific since the activity of adenylate cyclase, another marker of basolateral membranes, was not altered. Finally, when animals were adrenalectomized prior to streptozotocin treatment, Na-K-ATPase stimulation was curtailed in the collecting tubule but not in more proximal segments. These results suggest that diabetes alters Na-K-ATPase activity in specific nephron segments independent of alterations of glomerular filtration rate and of kidney hypertrophy, and that the stimulation of collecting tubule Na-K-ATPase is secondary to hyperaldosteronism.
Khadouri
C
C
Barlet-Bas
C
C
Doucet
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism; D000315:Adrenalectomy; D000450:Aldosterone / Q000097:blood; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology*; D005919:Glomerular Filtration Rate; D007684:Kidney Tubules / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D000450:Aldosterone; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase