Enhanced renal tubular ouabain-sensitive ATPase in streptozotocin diabetes mellitus

Abstract

The effect of streptozotocin-induced diabetes mellitus on rat renal ouabain-sensitive ATPase in six distinct nephron segments was studied. Twenty-four hours after administration of streptozotocin, blood glucose increased threefold (P less than 0.001), and glucosuria was evident. Aldosterone levels increased almost twofold (P less than 0.001). Ouabain-sensitive ATPase increased in the proximal segments PC (proximal convoluted tubule) and PS (proximal straight tubule) by 43 and 62%, respectively, (P less than 0.001) and CD (cortical collecting duct) ouabain-sensitive ATPase increased 77% (P less than 0.001). Ouabain-sensitive ATPase in the cortical (CTAL) and medullary (MTAL) thick ascending limbs of Henle's loop and in the DC (distal convoluted tubule) remained unchanged after 24 h of streptozotocin administration. Eight days after streptozotocin administration, when glomerular filtration rate (GFR) was already markedly elevated, ouabain-sensitive ATPase remained increased in the PC, PS, and CD but was significantly less compared with the activity after 24 h (P less than 0.05), whereas in the CTAL and MTAL a marked increase in ouabain-sensitive ATPase occurred by 54% in the CTAL and 65% in the MTAL (P less than 0.001). Aldosterone levels remained elevated compared with control but less than after 24 h. Pretreatment with deoxycorticosterone acetate abolished the increase in ouabain-sensitive ATPase in the CD. These findings show that streptozotocin-induced diabetes mellitus in the rat is associated with a substantial increase in ouabain-sensitive ATPase activity along most of the nephron. This increase in enzyme activity may represent a mechanism of physiological adaptation of the nephron to maintain electrolyte homeostasis in diabetes in face of the increased GFR and osmotic diuresis.

Renal Na-K-ATPase hyperactivity in diabetic Psammomys obesus is related to glomerular hyperfiltration but is insulin-independent

“…This verifies that this relationship is indeed real. These findings are similar to previous observations in rats with streptozotocin-induced diabetes mellitus (Wald & Popovtzer 1984, Wald et al 1986, Khaduri et al 1987. In the rat, Na-K-ATPase activity increased in the cortex and medulla parallel with an increase in GFR.…”

Quantitative morphology of the rat kidney during diabetes mellitus and insulin treatment

“…Growth factors, including insulin like growth factor, which possibly stimulate growth in the PT, are increased in diabetes [29,30]. The increased glomerular filtration rate imposes an extra workload on the tubules for reabsorption of filtered water and solutes, and the increased amount of Na,K-ATPase in the kidney in the STZ-diabetic kidney [31,32] confirms an increase in sodium absorption.…”

Rapid development of glomerulosclerosis in diabetic Dahl salt-sensitive rats

“…The DS rats which have been described as the animal model most closely resembling human hypertension [27], have an altered sodium metabolism that also predisposes to sodium retention, extracellular volume expansion and hypertension [12,28,29]. Diabetes increases proximal tubular Na + , K + ATPase activity in all species and rat strains studied [30][31][32][33][34]. High glucose concentration in the tubular fluid is mainly responsible for this increase [11].…”

“…In each study, we determined total ATPase activity and Mg-ATPase activity in six to eight segments. The phosphate released from [g- 32 P]ATP in six to eight samples of incubation solution containing no tubule segments was determined to correct for non-specific ATP hydrolysis. Na + , K + ATPase activity was calculated as the difference between the mean values for total ATPase activity and Mg-ATPase activity.…”