Glucose handling by the kidney Amanda Mather, Carol Pollock  Kidney International  Volume 79, Pages S1-S6 (March 2011) DOI: 10.1038/ki.2010.509 Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 1 Renal glycolysis and gluconeogenesis—pathway and enzyme localization. Glycolytic key enzymes (1) hexokinase, (2) phosphofructokinase, and (3) pyruvate kinase are predominantly localized in cells of the renal medulla. The key enzymes of gluconeogenesis, (4) pyruvate carboxylase, (5) phosphoenol pyruvate carboxykinase, (6) fructose-1,6-biphosphatase, and (7) glucose 6-phosphatase, are found mainly in renal cortical cells.8 Copyright 1997, Springer-Verlag. Kidney International 2011 79, S1-S6DOI: (10.1038/ki.2010.509) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 2 Urinary glucose excretion and tubular reabsorption as a function of filtered load. Tubular reabsorption increases linearly with filtered load as a part of glomerulotubular balance. When reabsorption reaches the tubular capacity (Tm glucose), glucose starts appearing in the urine. The plasma glucose concentration for the given glomerular filtration rate (GFR) is the glycosuric threshold.18 Copyright 2007, Saunders, an imprint of Elsevier. Kidney International 2011 79, S1-S6DOI: (10.1038/ki.2010.509) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 3 Relative magnitude of glucose transport characteristics in different segments of the proximal tubule.Jmax, maximal glucose transport rate; Km, affinity constant for glucose.18,21 Copyright 2007, Saunders, an imprint of Elsevier. Kidney International 2011 79, S1-S6DOI: (10.1038/ki.2010.509) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 4 Glucose reabsorption from the glomerular filtrate through tubule epithelial cells into blood.20,30 Copyright 2004, Int Union Physiol Sci/Am Physiol Soc. Kidney International 2011 79, S1-S6DOI: (10.1038/ki.2010.509) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 5 Glucose transporters in proximal tubules of rats. In the early proximal tubule (PCT), filtered luminal glucose and interstitial glucose are approximately equal. Sodium-dependent glucose transporter (SGLT2) functions to elevate intracellular glucose concentrations above interstitial levels. Transporters on the basolateral membrane of PCT epithelial cells include GLUT2, GLUT1, and Na-K-adenosinetriphosphatase (Na+-K+-ATPase). Under normoglycemic conditions there is an outward flow of glucose down a concentration gradient across the basolateral membrane via GLUT2. GLUT2 is unlikely to be saturated because of its relatively higher Km versus intracellular glucose concentrations, whereas GLUT1 may be saturated because of its relatively lower Km. In the lumen of the late proximal tubule (PST), the concentration of glucose is greatly reduced compared with the PCT, and is much lower than the interstitial glucose concentration. SGLTl functions to elevate intracellular glucose concentrations. The basolateral transporters in PST epithelial cells are GLUT1 and Na+-K+-ATPase. GLUT1 may be saturated because its Km may be close to interstitial glucose concentrations.32 Copyright 1994, Am Soc Nephrol. Kidney International 2011 79, S1-S6DOI: (10.1038/ki.2010.509) Copyright © 2011 International Society of Nephrology Terms and Conditions