Saving the sweetness: renal glucose handling in health and disease

Abstract

Glucose homeostasis is highly controlled, and the function of the kidney plays an integral role in this process. The exquisite control of blood glucose relies, in part, on renal glucose filtration, renal glucose reabsorption, and renal gluconeogenesis. Particularly critical to maintaining glucose homeostasis is the renal reabsorption of glucose; with ~162 g of glucose filtered by the kidney per day, it is imperative that the kidney have the ability to efficiently reabsorb nearly 100% of this glucose back in the bloodstream. In this review, we focus on this central process, highlighting the renal transporters and regulators involved in both the physiology and pathophysiology of glucose reabsorption.

Keywords: glucose reabsorption; glucose transporter 2; proximal tubule; sodium-glucose cotransporter 1; sodium-glucose cotransporter 2.

Fig. 1.

Glucose transporters and their regulators in the renal proximal tubule. Na⁺-glucose cotransporters Sglt1 and Sglt2 localize to the apical plasma (ap) membrane of the proximal tubule where they face the newly forming urine and use the existing Na⁺ gradient to reabsorb all filtered glucose. The Na⁺ gradient is maintained by the Na⁺-K⁺-ATPase (labeled Na⁺ pump) on the basolateral (BL) membrane. Glut1 and Glut2 localize to the BL plasma membrane where they function to release the reabsorbed and newly generated glucose back in circulation. Known regulators of the glucose transporters that are discussed in text are labeled in the proximal tubule segments in which they are known to be found. Diseases associated with the glucose transporters are also noted.