Increased renal metabolism in diabetes. Mechanism and functional implications.
The coupling between the Na+/glucose cotransporter and Na(+)-K(+)-ATPase (NKA) described for epithelial cells (1) prompted us to study in rats with streptozocin-induced diabetes the effect of increased tubular glucose load on tubular Na+ reabsorption, NKA-dependent O2 consumption (QO2), and NKA activity. Filtered glucose is mainly reabsorbed in the proximal tubuli via the phlorizin-sensitive Na+/glucose cotransporter. In this study, the diabetic rats had a significantly higher renal blood flow (RBF), glomerular filtration rate (GFR), and Na+ reabsorption than the control rats. Total renal QO2 as well as QO2 in cortical tissue, which consists mainly of proximal tubular cells, was significantly higher in diabetic than in control rats. The increase in tissue QO2 was entirely caused by increased NKA-dependent QO2. NKA activity, measured as rate of ATP hydrolysis, was increased in cortical tubular but not glomerular tissue from diabetic rats. Phlorizin treatment abolished the increase in NKA activity, Na+ reabsorption, and QO2, as well as the increase in RBF and GFR in diabetic rats. We conclude that diabetes is associated with increased renal O2 metabolism secondary to the increase in coupled Na+ reabsorption via the Na+/glucose cotransporter and NKA. The increased oxygen consumption might contribute to the hyperperfusion and hyperfiltration in the diabetic kidney.
Körner
A
A
Department of Pediatrics, Karolinska Institute, St. Göran's Children's Hospital, Stockholm, Sweden.
Eklöf
A C
AC
Celsi
G
G
Aperia
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D005919:Glomerular Filtration Rate; D007668:Kidney / Q000503:physiopathology; D007672:Kidney Cortex / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010101:Oxygen Consumption; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012079:Renal Circulation; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000378:metabolism*
D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D010042:Ouabain; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase