Glucose Clearance

Snapshot

• A 32-year-old obese woman with a history of PCOS presents to the physician because she is still unable to get pregnant despite usage of clomiphene citrate.  She states that she has been compliant with diet and exercise though she has gained 40 pounds since her last visit 2 months ago.  A urine dipstick is performed at this visit demonstrating glucose in the urine – a finding that was not present at her last visit.

Overview

• Glucose reabsorption
  • glucose is freely filtered across glomerular capillary into Bowman’s space
  • glucose is reabsorbed by epithelial cells of proximal convoluted tubule
    • apical (luminal) membrane of epithelial cells faces tubular fluid
      • contains Na⁺-glucose (SGLT) cotransporter 
    • basolateral (peritubular) membrane of epithelial cells faces peritubular capillary blood
      • contains Na⁺-K⁺ ATPase and facilitated glucose transporter (GLUT1, GLUT2)
• Mechanism of reabsorption
  • 2 Na⁺ and 1 glucose are transported from tubular fluid into epithelial cells via Na⁺ – glucose (SGLT) cotransporters
    • Na⁺-K⁺ ATPase establishes and maintains Na⁺ electrochemical gradient
    • downhill transport of 2 Na⁺ provides energy for uphill transport of 1 glucose (secondary active transport)
  • glucose is transported from epithelial cells into peritubular capillary blood via glucose transporters (GLUT1/2)
    • downhill transport of glucose (facilitated diffusion)
• Filtered load
  • filtered load = GFR x [P]_glucose
• Reabsorption
  • plasma [glucose] < 160 mg/dL
    • filtered load of glucose is completely reabsorbed
  • 160 mg/dL < plasma [glucose] < 200 mg/dL
    • filtered load of glucose is not completely reabsorbed
    • “threshold,” or plasma [glucose] at which glucose is first excreted in urine
  • plasma [glucose] > 350 mg/dL
    • filtered load of glucose is not completely reabsorbed
    • Na⁺ – glucose (SGLT) cotransporters are completely saturated
    • maximal glucose reabsorption (T_m)
• Glucosuria
  • excretion or “spilling” of glucose in urine
  • in uncontrolled diabetes mellitus, lack of insulin causes plasma [glucose] to increase to abnormally high levels
    • plasma [glucose] > T_m, as filtered load of glucose exceeds reabsorptive capacity