Homeostatic efficiency of tubuloglomerular feedback is reduced in established diabetes mellitus in rats

Abstract

We tested the hypothesis that the ability of the tubuloglomerular feedback (TGF) to stabilize renal function is impaired in rats with 7-8 wk of insulin-treated streptozotocin-diabetes. Proximal tubular flow was measured in free-flowing nephrons using a noninvasive optical technique. The homeostatic efficiency of TGF was determined from the fractional compensation for perturbations in ambient flow. Fractional compensation was substantially reduced in diabetic rats. To assess the roles of the proximal tubule and loop of Henle as determinants of TGF efficiency, we tested the effect of diabetes on proximal tubular reabsorption as determined by standard micropuncture and on the ionic content of early distal tubular fluid by employing a microelectrode for on-line measurement of electrical conductivity (TED). Diabetes caused glomerular hyperfiltration and increased fractional proximal tubular reabsorption (FPR), such that late proximal tubular flow (VLP) and early distal tubular flow were unaffected. The increase in FPR was a minor contributor to the overall effect on fractional compensation. Diabetes decreased the ambient TED without affecting the slope of the relationship between VLP and TED. These results demonstrate that the homeostatic, efficiency of the TGF system is reduced in diabetes and that this cannot be fully accounted for by changes in tubular reabsorption. Impaired TGF efficiency renders the diabetic glomerular microvasculature more susceptible to impact from fluctuat…