RENAL TUBULAR NA-K+-ATPASE IN DIABETES-MELLITUS - RELATIONSHIP TO METABOLIC ABNORMALITY()

This study was undertaken to evaluate the effect,of long-term diabetes on Na+-K+-ATPase in isolated nephron segments in five groups of rats: 1) controls of 7 wk duration (7 WD), 2) diabetes mellitus (DM) of 7 W D, 3) DM of 7 WD treated with insulin replacement, 4) DM rats of 25 WD , and 5) control rats of 25 WD. The blood glucose (BG) values in the f irst three groups were 123 +/- 9, 460 +/- 25, and 302 +/- 30 mg/dl; th e glomerular filtration rate (GFR) was 1.34 +/- 0.08, 1.80 +/- 0.10, a nd 1.77 +/-0.08 ml/min; and urinary sodium excretion was 0.94 +/- 0.05 ,1.76 +/- 0.10, and 1.40 +/- 0.07 mueq/min. Na+-K+-ATPase in group 2 i ncreased in all segments studied (P < 0.001, group 1 vs. 2 for all). I n group 3, Na+-K+-ATPase normalized in proximal convoluted (PC), proxi mal straight. (PS), and distal convoluted (DC) tubules (P < 0.001, gro up 2 vs. group 3 for all), whereas in the outer medullary thick ascend ing limb (OMTAL) the correction was partial and in the CTAL and CCD th ere was no correction. In group 4 BG was 420 +/- 20 mg/100 ml compared with 123 +/- 9 in group 5 (P < 0.001), and GFR was 1.19 +/- 0.11 ml/m in vs. 1.15 +/- 0.11 in group 5 (P = not significant). In group 4 Na+- K+-ATPase in the PC and PS was greater than in group 5 (P < 0.001) and similar to group 2; in OMTAL it was reduced compared with group 2 (P < 0.001) and similar to group 5. These results show that 1) in DM GFR rose and Na+-K+-ATPase increased in all segments, 2) partial correctio n of BG led to a decrease in Na+-K+-ATPase in PC, PS and in DC, 3) par tial correction of BG with elevated GFR did not alter the Na+-K+-ATPas e in the loop of Henle, 4) in rats with diabetes of 25 WD, whose BG re mained high but GFR declined to normal, Na+-K+-ATPase in PC and PS rem ained high, whereas it decreased in OMTAL.