Effects of endogenous and exogenous hyperglycemia on renal glucose transport in the rat.

As acute renal glucose loading requires intravenous infusion of a large quantity of hypertonic glucose solution, we performed free-flow micropuncture studies in nine streptozotocin diabetic rats to evaluate renal tubule glucose transport in hyperglycemic state and the results were compared with those of 10 normal rats in which comparable hyperglycemia was induced by exogenous glucose loading. Despite hyperglycemia with a mean plasma glucose concentration at 19.2 mmol/l, glomerulotubular balance in the proximal tubule of the diabetic rats was well maintained with a mean proximal tubule fluid-to-plasma inulin ratio at 2.08 +/- 0.15 as compared with that of the normal control at 2.16 +/- 0.11. Acute glucose loading in the normal rats raised plasma glucose to a similar mean of 19.6 mmol/l, significantly inhibited proximal fluid and glucose reabsorption, increased their reabsorption in the intermediate segment (between late proximal tubule and early distal tubule) and led to natriuresis and exaggerated glycosuria (fractional sodium excretion 1.32% and fractional glucose excretion 14.8% compared with 0.47% and 7.3%, respectively, for the diabetic control). Administration of insulin to normalize plasma glucose in the diabetic rats also inhibited proximal fluid and glucose reabsorption and resulted in modest natriuresis. This observation is consistent with the existence of sodium-glucose cotransport in the proximal tubule with sodium transport being reduced along with glucose transport following insulin administration. It is concluded that acute glucose loading, as performed in the conventional glucose titration study, leads to artifactual inhibition of proximal sodium and glucose transport.