GLUT8 is Dispensable for Embryonic Development but Influences Hippocampal Neurogenesis and Heart Function

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 May 18

PMID 16705176

Citations 33

Authors

Mathieu Membrez

Edith Hummler

Friedrich Beermann

Jacques-Antoine Haefliger

Rebecca Savioz

Thierry Pedrazzini

Bernard Thorens

Affiliations

Soon will be listed here.

Abstract

GLUT8 is a glucose transporter isoform expressed at high levels in testis; at intermediate levels in the brain, including the hippocampus; and at lower levels in the heart and several other tissues. GLUT8 is located in an intracellular compartment and does not appear to translocate to the cell surface, except in blastocysts, where insulin has been reported to induce its surface expression. Here, we generated mice with inactivation of the glut8 gene. We showed that expression of GLUT8 was not required for normal embryonic development and that glut8-/- mice had normal postnatal development, glucose homeostasis, and response to mild stress. Adult glut8-/- mice showed increased proliferation of hippocampal cells but no defect in memory acquisition and retention. Absence of GLUT8 from the heart did not alter heart size and morphology but led to an increase in P-wave duration, which was not associated with abnormal Nav1.5 Na+ channel or connexin expression. Thus, absence of GLUT8 expression in the mouse caused complex but mild physiological alterations.

Citing Articles

The Impact of SLC2A8 RNA Interference on Glucose Uptake and the Transcriptome of Human Trophoblast Cells.

Lipka A, Paukszto L, Kennedy V, Tanner A, Majewska M, Anthony R Cells. 2024; 13(5.

PMID: 38474355 PMC: 10930455. DOI: 10.3390/cells13050391.

Lysosomal glucose sensing and glycophagy in metabolism.

Mancini M, Noland R, Collier J, Burke S, Stadler K, Heden T Trends Endocrinol Metab. 2023; 34(11):764-777.

PMID: 37633800 PMC: 10592240. DOI: 10.1016/j.tem.2023.07.008.

Preimplantation or gestation/lactation high-fat diet alters adult offspring metabolism and neurogenesis.

Ojeda D, Hutton O, Hopkins R, Cagampang F, Smyth N, Fleming T Brain Commun. 2023; 5(2):fcad093.

PMID: 37033334 PMC: 10077335. DOI: 10.1093/braincomms/fcad093.

Brain insulin signaling and cognition: Possible links.

Yaribeygi H, Maleki M, Butler A, Jamialahmadi T, Sahebkar A EXCLI J. 2023; 22:237-249.

PMID: 36998706 PMC: 10043452. DOI: 10.17179/excli2023-5841.

Fetal Myocardial Expression of GLUT1: Roles of BPA Exposure and Cord Blood Exosomes in a Rat Model.

Ermini L, Mandala M, Cresti L, Passaponti S, Patrussi L, Paulesu L Cells. 2022; 11(20).

PMID: 36291063 PMC: 9601122. DOI: 10.3390/cells11203195.

References

van Praag H, Christie B, Sejnowski T, Gage F . Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A. 1999; 96(23):13427-31. PMC: 23964. DOI: 10.1073/pnas.96.23.13427. View

Widmer M, Uldry M, Thorens B . GLUT8 subcellular localization and absence of translocation to the plasma membrane in PC12 cells and hippocampal neurons. Endocrinology. 2005; 146(11):4727-36. DOI: 10.1210/en.2005-0668. View

Ibberson M, Uldry M, Thorens B . GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues. J Biol Chem. 2000; 275(7):4607-12. DOI: 10.1074/jbc.275.7.4607. View

Doege H, Schurmann A, Bahrenberg G, Brauers A, Joost H . GLUT8, a novel member of the sugar transport facilitator family with glucose transport activity. J Biol Chem. 2000; 275(21):16275-80. DOI: 10.1074/jbc.275.21.16275. View

Carayannopoulos M, Chi M, Cui Y, Pingsterhaus J, McKnight R, Mueckler M . GLUT8 is a glucose transporter responsible for insulin-stimulated glucose uptake in the blastocyst. Proc Natl Acad Sci U S A. 2000; 97(13):7313-8. PMC: 16542. DOI: 10.1073/pnas.97.13.7313. View

Ibberson M, Riederer B, Uldry M, Guhl B, Roth J, Thorens B . Immunolocalization of GLUTX1 in the testis and to specific brain areas and vasopressin-containing neurons. Endocrinology. 2001; 143(1):276-84. DOI: 10.1210/endo.143.1.8587. View

Reagan L, Rosell D, Alves S, Hoskin E, McCall A, Charron M . GLUT8 glucose transporter is localized to excitatory and inhibitory neurons in the rat hippocampus. Brain Res. 2002; 932(1-2):129-34. DOI: 10.1016/s0006-8993(02)02308-9. View

Pinto A, Carayannopoulos M, Hoehn A, Dowd L, Moley K . Glucose transporter 8 expression and translocation are critical for murine blastocyst survival. Biol Reprod. 2002; 66(6):1729-33. DOI: 10.1095/biolreprod66.6.1729. View

Dilaveris P, Gialafos J . Future concepts in P wave morphological analyses. Card Electrophysiol Rev. 2002; 6(3):221-4. DOI: 10.1023/a:1016320807103. View

10.

Kempermann G, Gage F . Genetic determinants of adult hippocampal neurogenesis correlate with acquisition, but not probe trial performance, in the water maze task. Eur J Neurosci. 2002; 16(1):129-36. DOI: 10.1046/j.1460-9568.2002.02042.x. View

11.

Shin B, McKnight R, Devaskar S . Glucose transporter GLUT8 translocation in neurons is not insulin responsive. J Neurosci Res. 2004; 75(6):835-44. DOI: 10.1002/jnr.20054. View

12.

Piroli G, Grillo C, Charron M, McEwen B, Reagan L . Biphasic effects of stress upon GLUT8 glucose transporter expression and trafficking in the diabetic rat hippocampus. Brain Res. 2004; 1006(1):28-35. DOI: 10.1016/j.brainres.2004.01.044. View

13.

Morris R . Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984; 11(1):47-60. DOI: 10.1016/0165-0270(84)90007-4. View

14.

Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9. DOI: 10.1006/abio.1987.9999. View

15.

Spinedi E, Giacomini M, Jacquier M, Gaillard R . Changes in the hypothalamo-corticotrope axis after bilateral adrenalectomy: evidence for a median eminence site of glucocorticoid action. Neuroendocrinology. 1991; 53(2):160-70. DOI: 10.1159/000125713. View

16.

Reis L, Ruffner H, Stark G, Aguet M, Weissmann C . Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes. EMBO J. 1994; 13(20):4798-806. PMC: 395418. DOI: 10.1002/j.1460-2075.1994.tb06805.x. View

17.

Widmann C, Dolci W, Thorens B . Agonist-induced internalization and recycling of the glucagon-like peptide-1 receptor in transfected fibroblasts and in insulinomas. Biochem J. 1995; 310 ( Pt 1):203-14. PMC: 1135874. DOI: 10.1042/bj3100203. View

18.

Dymecki S . Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice. Proc Natl Acad Sci U S A. 1996; 93(12):6191-6. PMC: 39212. DOI: 10.1073/pnas.93.12.6191. View

19.

Geering K, Beggah A, Good P, Girardet S, Roy S, Schaer D . Oligomerization and maturation of Na,K-ATPase: functional interaction of the cytoplasmic NH2 terminus of the beta subunit with the alpha subunit. J Cell Biol. 1996; 133(6):1193-204. PMC: 2120891. DOI: 10.1083/jcb.133.6.1193. View

20.

Rajewsky K, Gu H, Kuhn R, Betz U, Muller W, Roes J . Conditional gene targeting. J Clin Invest. 1996; 98(3):600-3. PMC: 507466. DOI: 10.1172/JCI118828. View