Journal Article

The Role of SGLT1 and GLUT2 in Intestinal Glucose Transport and Sensing

Röder, Pia V., Zietek, Tamara S., Geillinger, Kerstin E., Koepsell, Hermann, Daniel, Hannelore, Thorens, Bernard

2014

Overview

Intestinal glucose absorption is mediated by SGLT1 whereas GLUT2 is considered to provide basolateral exit. Recently, it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion. Moreover, SGLT1 and GLUT2 are suggested to play an important role in intestinal glucose sensing and incretin secretion. In mice that lack either SGLT1 or GLUT2 we re-assessed the role of these transporters in intestinal glucose uptake after radiotracer glucose gavage and performed Western blot analysis for transporter abundance in apical membrane fractions in a comparative approach. Moreover, we examined the contribution of these transporters to glucose-induced changes in plasma GIP, GLP-1 and insulin levels. In mice lacking SGLT1, tissue retention of tracer glucose was drastically reduced throughout the entire small intestine whereas GLUT2-deficient animals exhibited higher tracer contents in tissue samples than wild type animals. Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose. In mice lacking GLUT2, glucose-induced insulin but not incretin secretion was impaired. Western blot analysis revealed unchanged protein levels of SGLT1 after glucose gavage. GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration. SGLT1 is unequivocally the prime intestinal glucose transporter even at high luminal glucose concentrations. Moreover, SGLT1 mediates glucose-induced incretin secretion. Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Absorption / Animals / Biology / Blood glucose / Blood Glucose - metabolism / Bulk transporters / Chemoreception / Contamination / Glucose / Glucose - metabolism / Glucose - pharmacology / Glucose transport / Glucose transporter / Glucose Transporter Type 2 - deficiency / Glucose Transporter Type 2 - metabolism / Incretins - blood / Incretins - metabolism / Insulin / Insulin - blood / Insulin - metabolism / Insulin Secretion / Intestinal Absorption - drug effects / Intestinal Mucosa - metabolism / Intestines - drug effects / Kinases / Membranes / Mice / Radioactive tracers / Rodents / Secretion / Small intestine / Sodium-Glucose Transporter 1 - deficiency / Sodium-Glucose Transporter 1 - metabolism / Tracers (Biology)