GLUT-1

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GLUT-1
GLUT-1
Ribbon model of the human glucose transporter GLUT-1 with β-nonylglucoside as ligand , according to PDB  4PYP

Existing structural data : 5EQI

Properties of human protein
Mass / length primary structure 492 amino acids
Secondary to quaternary structure Homotetramer; multipass (12 TMS) membrane protein
Identifier
Gene names SLC2A1  ; GLUT1
External IDs
Transporter classification
TCDB 2.A.1.1.28
designation Major facilitator superfamily / glucose transporter
Occurrence
Parent taxon Mammals
Orthologue
human House mouse
Entrez 6513 20525
Ensemble ENSG00000117394 ENSMUSG00000028645
UniProt P11166 P17809
Refseq (mRNA) NM_006516 NM_011400
Refseq (protein) NP_006507 NP_035530
Gene locus Chr 1: 42.93 - 42.96 Mb Chr 4: 119.11 - 119.14 Mb
PubMed search 6513 20525

GLUT-1 , also known as erythrocyte / brain hexose facilitator ( gene : SLC2A1 ), is a transport protein in the cell membrane of the β cells of the pancreas , cells of the blood-brain barrier of mammals and many other types of tissue, which is responsible for the transport of glucose , but also other pentoses and hexoses , as well as vitamin C through the cell membrane.

Mutations in the SLC2A1 gene can cause the GLUT1 deficit syndrome .

function

GLUT-1 occurs in most types of tissue; it enables glucose to be supplied independently of insulin .

In the central nervous system , it is essential for glucose uptake, and it also transports glucose across the membrane of β cells in the human pancreas.

The transport equation is:

Solute outside ⇔ Solute inside

So it is a uniport. Preferred solutes are D- glucose, dehydroascorbic acid and quercetin. At the same time, water can diffuse through a parallel channel. A sliding process across multiple binding sites has been proposed for glucose transport. The switch to dehydroascorbate transport in erythrocytes takes place by means of the membrane protein stomatin and this process only occurs in those mammals that cannot produce ascorbic acid themselves.

Medical importance

In animal models of diabetes mellitus , the expression of GLUT1 in cardiac muscle tissue and in vessels of the retina is reduced . Patients with type 2 diabetes mellitus show a reduced expression of GLUT1 and a reduced glucose uptake in skeletal muscle cells . In contrast, in diabetics there is an increased expression of GLUT1 in the mesangium cell of the kidney corpuscle . This causes an increased uptake of glucose in the kidneys and an excessive activation of glucose-dependent metabolic pathways. This ultimately leads to an increased formation of TGF-β . This upregulation of TGF-β promotes the excessive production of extracellular matrix , which is viewed as a possible cause of diabetic kidney damage . In addition, TGF-β promotes the expression of GLUT1 and thus maintains the pathomechanism .

An increased pressure in the capillaries of the kidney corpuscle or an increase in angiotensin II also promotes the expression of GLUT1 in the kidney. This mechanism may be a cause of kidney damage (nephrosclerosis) caused by high blood pressure or obesity .

A congenital defect of the SLC2A1 - gene can GLUT1 deficiency lead ( GLUT1 deficiency syndrome ). Due to the insufficient supply of the brain with glucose as the only fuel, it leads to a significant delay in physical and mental development, epilepsy and a head circumference that is not growing (acquired microcephalus), in about half of the children affected it also leads to a balance disorder ( ataxia ) and decreased muscle strength (muscular hypotension).

GLUT-1 is a docking point for the HTLV . Variants of GLUT-1 are associated with diabetic nephropathy in diabetes mellitus . GLUT-1 is overexpressed in several cancer cell lines.

regulation

GSK-3 is obviously involved in the regulation of glucose uptake and the expression of GLUT-1 , via modulation by TSC2 and mTOR .

Web links

Individual evidence

  1. ↑ InterPro: IPR002439 Glucose transporter, type 1 (GLUT1) ( Memento from May 25, 2008 in the Internet Archive )
  2. ↑ Löffler, Petrides: Biochemistry and Pathobiochemistry . Ed .: Lutz Graeve. 9th edition. Springer, 2014, ISBN 978-3-642-17972-3 , pp. 199-200 .
  3. ↑ UniProt P11166
  4. ↑ Suls A, Dedeken P, Goffin K, et al : Paroxysmal exercise-induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1 . In: Brain . 131, No. Pt 7, July 2008, pp. 1831-44. doi : 10.1093 / brain / awn113 . PMID 18577546 . PMC 2442425 (free full text).
  5. ↑ Löffler / Petrides "Biochemie und Pathobiochemie" 9th edition, p. 445
  6. ↑ KT Coppieters, A. Wiberg, N. Amirian, TW Kay, MG von Herrath: Persistent glucose transporter expression on pancreatic beta cells from longstanding type 1 diabetic individuals. In: Diabetes / metabolism research and reviews. Volume 27, Number 8, November 2011, pp. 746-754, doi : 10.1002 / dmrr.1246 , PMID 22069254 .
  7. ↑ TCDB : 2.A.1
  8. ↑ Cunningham P, Afzal-Ahmed I, Naftalin RJ: Docking studies show that D-glucose and quercetin slide through the transporter GLUT1 . In: J. Biol. Chem. . 281, No. 9, March 2006, pp. 5797-803. doi : 10.1074 / jbc.M509422200 . PMID 16407180 .
  9. ↑ Montel-Hagen A, S Kinet, Manel N, et al : Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C . In: Cell . 132, No. 6, March 2008, pp. 1039-48. doi : 10.1016 / j.cell.2008.01.042 . PMID 18358815 .
  10. Jump up ↑ Luigi Gnudi et al .: Mechanical Forces in Diabetic Kidney Disease: A Trigger for Impaired Glucose Metabolism . In: J Am Soc Nephrol . No. 18 , 2007, p. 2226-2232 ( abstract ).
  11. ↑ Kepler et al .: Congenital disorders of glucose transport. In: Monthly Kinderheilkunde 2000 148: 2–11
  12. ↑ Manel N, Kim FJ, Kinet S, Taylor N, Sitbon M, Battini JL: The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV . In: Cell . 115, No. 4, November 2003, pp. 449-59. PMID 14622599 .
  13. ↑ Afonso PV, Ozden S, Cumont MC, et al : Alteration of blood-brain barrier integrity by retroviral infection . In: PLoS Pathog . . 4, No. 11, November 2008, p. E1000205. doi : 10.1371 / journal.ppat.1000205 . PMID 19008946 . PMC 2575404 (free full text).
  14. ↑ Makni K, Jarraya F, Rebaï M, et al : Risk genotypes and haplotypes of the GLUT1 gene for type 2 diabetic nephropathy in the Tunisian population . In: Ann. Hum. Biol . 35, No. 5, 2008, pp. 490-8. doi : 10.1080 / 03014460802247142 . PMID 18821326 .
  15. ↑ Ahrens WA, Ridenour RV, Caron BL, Miller DV, Folpe AL: GLUT-1 expression in mesenchymal tumors: an immunohistochemical study of 247 soft tissue and bone neoplasms . In: Hum. Pathol. . 39, No. 10, October 2008, pp. 1519-26. doi : 10.1016 / j.humpath.2008.03.002 . PMID 18620729 .
  16. ↑ Li J, Yang SJ, Zhao XL, et al : [Significant increase in glucose transport activity in breast cancer] . In: Zhonghua Bing Li Xue Za Zhi . 37, No. 2, February 2008, pp. 103-8. PMID 18681321 .
  17. ↑ Buller CL, Loberg RD, Fan MH, et al : A GSK-3 / TSC2 / mTOR pathway regulates glucose uptake and GLUT1 glucose transporter expression . In: Am. J. Physiol., Cell Physiol. . 295, No. 3, September 2008, pp. C836-43. doi : 10.1152 / ajpcell.00554.2007 . PMID 18650261 .