title: Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption.
abstract: An increase in Na+/glucose cotransport upstream to the macula densa might contribute to the increase in single nephron GFR (SNGFR) in early diabetes mellitus by lowering the signal of the tubuloglomerular feedback, i.e., the luminal Na+, Cl-, and K+ concentration sensed by the macula densa. To examine this issue, micropuncture experiments were performed in nephrons with superficial glomeruli of streptozotocin-induced diabetes mellitus in rats. First, in nondiabetic control rats, ambient early distal tubular concentrations of Na+, Cl-, and K+ were about 21, 20, and 1.2 mM, respectively, suggesting collection sites relatively close to the macula densa. Second, glomerular hyperfiltration in diabetic rats was associated with a reduction in ambient early distal tubular concentrations of Na+, Cl-, and K+ by 20 to 28%, reflecting an increase in fractional reabsorption of these ions up to the early distal tubule. Third, in diabetic rats, early proximal tubular application of phlorizin, an inhibitor of Na+/glucose cotransport, elicited (1) a greater reduction in absolute and fractional reabsorption of Na+, Cl-, and K+ up to the early distal tubule, and (2) a greater increase in early distal tubular concentration of these ions, which was associated with a more pronounced reduction in SNGFR. These findings support the concept that stimulation of tubular Na+/glucose cotransport by reducing the tubuloglomerular feedback signal at the macula densa may contribute to glomerular hyperfiltration in diabetic rats. Glomerular hyperfiltration in diabetic rats serves to compensate for the rise in fractional tubular reabsorption to partly restore the electrolyte load to the distal nephron.
authors.affiliation: Department of Pharmacology, University of Tübingen, Germany. volker.vallon@uni-tuebingen.de
authors.forename: V
authors.initials: V
authors.lastname: Vallon
authors.forename: K
authors.initials: K
authors.lastname: Richter
authors.forename: R C
authors.initials: RC
authors.lastname: Blantz
authors.forename: S
authors.initials: S
authors.lastname: Thomson
authors.forename: H
authors.initials: H
authors.lastname: Osswald
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002712:Chlorides / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005246:Feedback; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006874:Hydrostatic Pressure; D007678:Kidney Glomerulus / Q000503:physiopathology*; D007684:Kidney Tubules / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008954:Models, Biological; D009399:Nephrons / Q000503:physiopathology; D010695:Phlorhizin / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism
chemical_list: D002712:Chlorides; D012964:Sodium; D010695:Phlorhizin; D005947:Glucose; D011188:Potassium