SY 10-1 RENAL GLUCOSE HANDLING AND SGLT2

Abstract

The kidneys maintain glucose homeostasis through its utilization, gluconeogenesis, and reabsorption. Glucose is freely filtered and reabsorbed in order to retain energy essential between meals. The amount of glucose reabsorbed by the kidneys is equivalent to the amount entering the filtration system. With a daily glomerular filtration rate of 180 L, approximately 180 g (180 L/day × 100 mg/dL) of glucose must be reabsorbed each day to maintain an average fasting plasma glucose concentration of 5.6 mmol/L (100 mg/dL). The reabsorption increases with increase in plasma glucose concentration up to approximately 11 mmol/L (198 mg/dL). At this threshold level, the system becomes saturated and the maximal resabsorption rate-the glucose transport maximum (Tm G ) is reached. No more glucose can be absorbed, and the kidneys begin excreting it in the urine-the beginning of glycosuria. Reabsorption of glucose occurs mainly in the proximal tubule and is mediated by 2 different transport proteins, Sodium Glucose Cotransporter (SGLT)1 and SGLT2. SGLT1, which are found in the straight section of the proximal tubule (S3), are responsible for approximately 10% of glucose reabsorption. The other 90% of filtered glucose is reabsorbed through by SGLT2, which are located in the convoluted section on the proximal tubule (S1). The SGLT2 are located on the luminal side of the early proximal tubule S1 segment. Absorption of sodium across the cell membrane creates an energy gradient that in turn allows glucose to be absorbed. On the other side of the cell, sodium is reabsorbed through sodium-potassium ATPase pump into the bloodstream. The concentration gradient within the cell, resulting from this exchange drives glucose reabsorption into the bloodstream via the Glucose transporter (GLUT) 2. The role of kidneys in glucose regulation has been well recognized in the recent years, and inhibition of glucose reabsorption by SGLT2 inhibitors has evolved as a promising target for therapeutic intervention in diabetes mellitus and an added benefit in hypertension.