Intestinal Absorption Of Glucose In Mice As Determined By Positron Emission Tomography

The current model of intestinal absorption is that SGLT1 is responsible for transport of glucose from the lumen into enterocytes across the brush border membrane, and GLUT2 for the downhill transport from the epithelium into blood across the basolateral membrane. Nevertheless, questions remain about the importance of these transporters in vivo. To address these questions, we have developed a non-invasive imaging method, positron emission tomography (PET), to monitor intestinal absorption of three non-metabolized glucose tracers during standard oral glucose tolerance tests (OGTTs) in mice. One tracer is specific for SGLTs (alpha-methyl-4-[F-18]fluoro-4-deoxy-D-glucopyranoside; Me-4FDG), one is specific for GLUTs (2-deoxy-2-[F-18] fluoro-D-glucose; 2-FDG), and one is a substrate for both SGLTs and GLUTs (4-deoxy-4-[F-18] fluoro-D-glucose; 4-FDG). OGTTs were conducted on adult wild-type, Sglt1(-/-) and Glut2(-/-) mice. In conscious mice, OGTTs resulted in the predictable increase in blood glucose that was blocked by phlorizin in both wild-type and Glut2(-/-) animals. The blood activity of both Me-4FDG and 4-FDG, but not 2-FDG, accompanied the changes in glucose concentration. PET imaging during OGTTs further shows that: (i) intestinal absorption of the glucose load depends on gastric emptying; (ii) SGLT1 is important for the fast absorption; (iii) GLUT2 is not important in absorption; and (iv) oral phlorizin reduces absorption by SGLT1, but is absorbed and blocks glucose reabsorption in the kidney. We conclude that in standard OGTTs in mice, SGLT1 is essential in fast absorption, GLUT2 does not play a significant role, and in the absence of SGLT1 the total load of glucose is slowly absorbed.