The Role of Kidney in Glucose Homeostasis — SGLT2 Inhibitors, a New Approach in Diabetes Treatment

Vasileios Andrianesis; John Doupis


Expert Rev Clin Pharmacol. 2013;6(5):519-539. 

In This Article

Tubular Glucose Reabsorption

Glucose Reabsorption Physiology

Apart from renal cortex glucose uptake and renal medulla gluconeogenesis, the role of glucose reabsorption in renal tubules is crucial for glucose homeostasis from kidneys. Under normal circumstances, the molecule of glucose is freely filtered from the glomerular capillary membrane and consequently all the amount of blood glucose passes from Bowman's capsule into the tubules.[21] Consequently, if plasma glucose normal concentration is 1 g/l and glomerular filtration rate (GFR) is about 180 l/day, the amount of the filtered glucose is about 180 g/day (or 125 mg/min). Virtually, none of the filtered glucose is normally excreted in the urine; therefore, the tubules have the ability to reabsorb over 180 g glucose per day. This mechanism, which allows the retention of valuable substances like glucose and amino acids, is facilitated by the combination of secondary active glucose transporters and passive glucose diffusion. The SGLTs Na+/D-glucose co-transporters (secondary active transporters) are located at the luminal membrane of the tubular cells.[21] The energy needed for glucose transportation against its electrochemical gradient (from the tubular lumen into the tubular cells) comes from the sodium ions diffusion. The low intracellular sodium concentration and the negative intracellular electrical potential, which allows the sodium diffusion down its electrochemical gradient through the luminal membrane of the tubular cells, are created from the sodium–potassium ATPase. This active transporter, located at the basolateral sides of the tubular epithelial cell, hydrolyzes ATP and uses the released energy for the transportation of sodium ions out of the cell into the interstitium. This mechanism is responsible for the low sodium concentration and the negative potential of the tubular cells. After entering the cells, glucose exits across the basolateral membranes by facilitated diffusion down its electrochemical gradient.[21]