• Typical plasma glucose concentration is between 70-100 milligrams/deciliters.
• Glucose is completely reabsorbed from the proximal tubule via secondary active transport mechanisms as long as plasma glucose concentrations do not exceed this concentration.

REABSORPTION

• Sodium-potassium ATPase extrudes sodium from the cell in exchange for potassium.
  – This exchange creates the electrochemical gradient that drives the SGLT co-transportation of sodium and glucose into the cell.
• As sodium moves down its concentration gradient, glucose moves against its concentration gradient.
• From here, GLUT transporters facilitate glucose diffusion out of the cell to return it to the blood (again, there are multiple types of GLUT transporters, but here we’ll simply generalize).
  – Within the healthy physiological glucose range, these transporters can completely reabsorb glucose from the proximal tubule; however, as we’ll see, at higher plasma concentrations, the transporters are overwhelmed, glucose is incompletely reabsorbed, and thus is excreted in the urine.

GLUCOSE TITRATION CURVE

Explains relationships between glucose plasma concentration, reabsorption, and excretion.

• Filtered load of glucose increases in proportion to plasma glucose levels; this makes sense, because we know that glucose is freely filtered within the renal corpuscle. (A)
• Glucose reabsorption follows filtration until plasma glucose concentration reaches approximately 200 milligrams per deciliter. (B)
  – At that point, the glucose reabsorption curve begins to bend because glucose transporters are approaching saturation.
• At plasma glucose concentrations above 350 milligrams per deciliter, glucose reabsorption plateaus as the transporters reach full saturation. (D)
• Glucose excretion remains near zero until glucose plasma concentration rises above 200 milligrams per deciliter (C)
  – Once this threshold is surpassed, glucose begins to appear in the urine (aka, glucosuria).
• Then, when plasma glucose concentration rises above of 350-400 milligrams per deciliter, excretion rises in parallel with filtered load. (E)

Summary of some key points in the glucose titration curve.

• Filtered load increases in proportion to plasma glucose concentrations (even when outside of the typical physiological range).
• Reabsorption matches filtered load when plasma glucose concentrations remain below 200 milligrams per deciliter.
• Above this threshold, glucose begins to appear in the urine (aka, glucosuria).
• Once plasma glucose concentration rises above 350 milligrams per deciliter, all glucose transporters are saturated.
• Transport maximum (Tm) is reached, and glucose reabsorption plateaus.
• Once transport maximum is reached, excretion rate rises linearly with filtered load.
• Because of a phenomenon called splay, threshold occurs before Tm because of variation in the transport maximum of individual nephrons due to differences in transport number and types.

Clinical causes of glucosuria.

• Glucosuria occurs when the filtered load of glucose exceeds the resorptive capabilities, and glucose is excreted in the urine.
• Diabetes mellitus, the body’s inability to make and/or use insulin results in excessive plasma glucose concentrations, which increases its filtered load.
• Some women experience pregnancy-related glucosuria when increased GFR increases filtered load. This is often benign, and is not synonymous with gestational diabetes.