| Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. | |
| | |
MedLine Citation:
|
PMID: 20980548 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The human Na(+)/D-glucose cotransporter 2 (hSGLT2) is believed to be responsible for the bulk of glucose reabsorption in the kidney proximal convoluted tubule. Since blocking reabsorption increases urinary glucose excretion, hSGLT2 has become a novel drug target for Type 2 diabetes treatment. Glucose transport by hSGLT2 was studied at 37°C in human embryonic kidney 293T cells using whole cell patch-clamp electrophysiology. We compared hSGLT2 with hSGLT1, the transporter in the straight proximal tubule (S3 segment). hSGLT2 transports with surprisingly similar glucose affinity and lower concentrative power than hSGLT1: Na(+)/D-glucose cotransport by hSGLT2 was electrogenic with apparent glucose and Na(+) affinities of 5 and 25 mM, and a Na(+):glucose coupling ratio of 1; hSGLT1 affinities were 2 and 70 mM and coupling ratio of 2. Both proteins showed voltage-dependent steady-state transport; however, unlike hSGLT1, hSGLT2 did not exhibit detectable pre-steady-state currents in response to rapid jumps in membrane voltage. D-Galactose was transported by both proteins, but with very low affinity by hSGLT2 (≥100 vs. 6 mM). β-D-Glucopyranosides were either substrates or blockers. Phlorizin exhibited higher affinity with hSGLT2 (K(i) 11 vs. 140 nM) and a lower Off-rate (0.03 vs. 0.2 s⁻¹) compared with hSGLT1. These studies indicate that, in the early proximal tubule, hSGLT2 works at 50% capacity and becomes saturated only when glucose is ≥35 mM. Furthermore, results on hSGLT1 suggest it may play a significant role in the reabsorption of filtered glucose in the late proximal tubule. Our electrophysiological study provides groundwork for a molecular understanding of how hSGLT inhibitors affect renal glucose reabsorption. |
| | |
Authors:
|
Charles S Hummel; Chuan Lu; Donald D F Loo; Bruce A Hirayama; Andrew A Voss; Ernest M Wright |
Related Documents
:
|
6686158 - Identification and characterization of the rat adipocyte glucose transporter by photoaf... 3510568 - Multiple tracer dilution estimates of d- and 2-deoxy-d-glucose uptake by the heart. 17943018 - Effect of long-term type 1 diabetes on renal sodium and water transporters in rats. 10896908 - Effect of proinflammatory interleukins on jejunal nutrient transport. 11544608 - Cardiac sympathetic innervation and blood flow regulation of the diabetic heart. 18194928 - Clinical efficacy and patient satisfaction with u-500 insulin pump therapy in patients ... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-27 |
Journal Detail:
|
Title: American journal of physiology. Cell physiology Volume: 300 ISSN: 1522-1563 ISO Abbreviation: Am. J. Physiol., Cell Physiol. Publication Date: 2011 Jan |
Date Detail:
|
Created Date: 2010-12-29 Completed Date: 2011-02-04 Revised Date: 2012-01-02 |
Medline Journal Info:
|
Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: United States |
Other Details:
|
Languages: eng Pagination: C14-21 Citation Subset: IM |
Affiliation:
|
Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1751, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Action Potentials Biological Transport, Active Carbon Isotopes / metabolism Gene Expression Regulation / physiology Glucose / metabolism* HEK293 Cells Humans Kidney / physiology* Methylglucosides / metabolism Phlorhizin / pharmacology Sodium-Glucose Transporter 1 / genetics, metabolism* Sodium-Glucose Transporter 2 / genetics, metabolism* Thermodynamics |
| Grant Support | |
ID/Acronym/Agency:
|
DK-019567/DK/NIDDK NIH HHS; DK-082153/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Carbon Isotopes; 0/Methylglucosides; 0/SLC5A1 protein, human; 0/SLC5A2 protein, human; 0/Sodium-Glucose Transporter 1; 0/Sodium-Glucose Transporter 2; 25360-07-0/methylglucoside; 50-99-7/Glucose; 60-81-1/Phlorhizin |
| Comments/Corrections | |
Comment In:
|
Am J Physiol Cell Physiol. 2011 Jan;300(1):C6-8
[PMID:
21048164
]
|
Erratum In:
|
Am J Physiol Cell Physiol. 2011 Mar;300(3):C721 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Potentiation of synaptic AMPA receptors induced by the deletion of NMDA receptors requires the GluA2...
Next Document: Posttranscriptional mechanisms involving microRNA-27a and b contribute to fast-specific and glucocor...