KEY POINTS - Glucose transporters are central players in glucose homeostasis. There are two major classes of glucose transporters in the body, the passive (GLUTs) and the secondary active or sodium-coupled transporters (SGLTs).
Here we report the use of a non-invasive imaging technique, Positron Emission Tomography (PET) in mice, to evaluate the role of GLUTs and SGLTs in controlling glucose distribution and utilization. We show that GLUTs are most significant for glucose in uptake into the brain and liver while SGLTs are important in glucose recovery in the kidney. This work provides further support to the use of SGLT imaging to study the role of SGLT transporters in human physiology and diseases such as diabetes and cancer.
ABSTRACT - The importance of SGLTs and GLUT2 in glucose homeostasis was studied in mice using fluorine-18 labelled glucose molecular imaging probes and non-invasive PET imaging. The probes were: Me-4FDG, a substrate for SGLTs; 4-FDG, a substrate for SGLTs and GLUTs; and 2-FDG, a substrate for GLUTs. These radiolabelled imaging probes were injected intravenously into wild-type, Sglt1(-/-) , Sglt2(-/-) and Glut2(-/-) mice and their dynamic whole-body distribution was determined using microPET. The distribution of 2-FDG was similar to that reported earlier, i.e. it accumulated in brain, heart, liver, and kidney and was excreted into the urinary bladder. There were little changes in 2-FDG distribution in Glut2(-/-) mice apart from a reduction in the rate of uptake into liver. The major differences between Me-4FDG and 2-FDG were that Me-4FDG did not enter the brain and was not excreted into the urinary bladder. There was urinary excretion of Me-4FDG in Sglt1(-/-) and Sglt2(-/-) mice. However, Me-4FDG was not reabsorbed in the kidney in Glut2(-/-) mice. There were no differences in Me-4FDG uptakes into heart of wild-type, Sglt1(-/-) and Sglt2(-/-) mice. We conclude that GLUT2 is important in glucose liver transport and reabsorption of glucose in the kidney along with SGLT2 and SGLT1. Complete reabsorption of Me-4FDG from the glomerular filtrate in wild-type mice and the absence of reabsorption in the kidney in Glut2(-/-) mice confirm the importance of GLUT2 in glucose absorption across the proximal tubule. This article is protected by copyright. All rights reserved.
The Journal of physiology. 2016 Mar 28 [Epub ahead of print]
Monica Sala-Rabanal, Bruce A Hirayama, Chiara Ghezzi, Jie Liu, Sung-Cheng Huang, Vladimir Kepe, Hermann Koepsell, Amy Yu, David R Powell, Bernard Thorens, Ernest M Wright, Jorge R Barrio
The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751., The Department of Physiology and the Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA, 90095-1751.