Nature 342, 798 - 800 (14 December 1989); doi:10.1038/342798a0

Expression of an insulin-regulatable glucose carrier in muscle and fat endothelial cells

Senen Vilaró^*, Manuel Palacín^†, Paul F. Pilch^‡, Xavier Testar^† & Antonio Zorzano^†§

^*Unitat de Biologia Cellular and ^†Unitat de Bioquimica i Biologia Molecular B, Departament de Bioquimica i Fisiologia, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028 Barcelona, Spain
^‡Department of Biochemistry, Boston University Medical School, 80 East Concord Street, Boston, Massachusetts 02118, USA
^§To whom correspondence should be addressed.

INSULIN rapidly stimulates glucose use in the major target tissues, muscle and fat, by modulating a tissue-specific glucose transporter isoform^1–6. Access of glucose to the target tissue is restricted by endothelial cells which line the walls of nonfenestrated capillaries of fat and muscle⁷. Thus, we examined whether the capillary endothelial cells are actively involved in the modulation of glucose availability by these tissues. We report here the abundant expression of the muscle/fat glucose transporter isoform in endothelial cells, using an immunocytochemical analysis with a monoclonal antibody specific for this isoform¹. This expression is restricted to endothelial cells from the major insulin target tissues, and it is not detected in brain and liver where insulin does not activate glucose transport. The expression of the muscle/fat transporter isoform in endothelial cells is significantly greater than in the neighbouring muscle and fat cells. Following administration of insulin to animals in vivo, there occurs a rapid increase in the number of muscle/fat transporters present in the lumenal plasma membrane of the capillary endothelial cells. These results document that insulin promotes the translocation of the muscle/fat glucose transporter in endothelial cells. It is therefore likely that endothelial cells play an important role in the regulation of glucose use by the major insulin target tissues in normal and diseased states.

References

1.	James, D. E., Brown, R., Navarro, J. & Pilch, P. F. Nature 333, 183−185 (1988). | Article | PubMed | ChemPort |
2.	James, D. E., Strube, M. & Mueckler, M. Nature 338, 83−87 (1989). | Article | PubMed | ChemPort |
3.	Birnbaum, M. J. Cell 57, 305−315 (1989). | Article | PubMed | ChemPort |
4.	Charron, M. J., Brosius, F. C., Alper, S. L. & Lodish, H. F. Proc. natn. Acad. Sci. U.S.A. 86, 2535−2539 (1989). | ChemPort |
5.	Kaestner, K. H. et al. Proc. natn. Acad. Sci. U.S.A. 86, 3150−3154 (1989). | ChemPort |
6.	Fukumoto, H. et al. J. biol. Chem. 264, 7776−7779 (1989). | PubMed | ChemPort |
7.	Karnovsky, M. G. in Capillary Permeability (eds Crone, C. & Lassen, N. A.) (Academic, New York, 1970).
8.	Andersson, L. & Lundahl, P. J. biol. Chem. 263, 11414−11420 (1988). | PubMed | ChemPort |
9.	Kalaria, R. N., Gravina, S. A., Schmidley, J. W., Perry, G. & Harik, S. I. Ann. Neurol. 24, 757−764 (1988). | Article | PubMed | ChemPort |
10.	Berger, J. et al. Nature 340, 70−72 (1989). | Article | PubMed | ChemPort |
11.	Zorzano, A. et al. J. biol. Chem. 264, 12358−12363 (1989). | PubMed | ChemPort |
12.	Garvey, W. T., Huecksteadt, T. P. & Birnbaum, M. J. Science 245, 60−63 (1989). | PubMed | ChemPort |
13.	Kahn, B. B., Charron, M. J., Lodish, H. F., Cushman, S. W. & Flier, J. S. J. clin. Invest. 84, 404−411 (1989). | PubMed | ChemPort |
14.	Hoyer, L. W., de los Santos, R. P. & Hoyer, J. R. J. clin Invest. 52, 2737−2744 (1973). | PubMed | ISI | ChemPort |
15.	Fukumoto, H. et al. Proc. natn. Acad. Sci. U.S.A. 85, 5434−5438 (1988). | ChemPort |
16.	Thorens, B., Sarkar, H. K., Kaback, H. R. & Lodish, H. F. Cell 55, 281−290 (1988). | Article | PubMed | ISI | ChemPort |
17.	Cushman, S. W. & Wardzala, L. J. J. biol. Chem. 255, 4758−4762 (1980). | PubMed | ISI | ChemPort |
18.	Suzuki, K. & Kono, T. Proc. natn. Acad. Sci. U.S.A. 77, 2542−2545 (1980). | ChemPort |
19.	Bar, R. S., Hoak, J. C. & Peacock, M. L. J. clin. Endocrin. Metab. 47, 699−702 (1978). | ChemPort |
20.	Jialal, I. et al. Endocrinology 117, 1222−1229 (1985). | PubMed | ChemPort |
21.	King, G. L. et al. J. clin. Invest. 71, 974−979 (1983). | PubMed | ChemPort |
22.	Bar, R. S., Siddle, K., Dolash, S., Boes, M. & Drake, B. Metabolism 37, 714−720 (1988). | Article | PubMed | ChemPort |
23.	King, G. L. & Johnson, S. Science 227, 1583−1586 (1985). | PubMed | ChemPort |
24.	Yang, Y. J., Hope, I. D., Ader, M. & Bergman, R. N. J. clin. Invest. 84, 1620−1628 (1989). | PubMed | ChemPort |
25.	Lithell, H. et al. Diabetes 30, 19−25 (1981). | PubMed | ChemPort |
26.	Lindgarde, E., Erickson, K. F., Lithell, H. & Saltin, B. Acta Med. Scand. 212, 99−106 (1982). | PubMed |
27.	Lillioja, S. et al. J. clin. Invest. 80, 415−424 (1987). | PubMed | ChemPort |
28.	Kwok, C. F. et al. J. clin. Invest. 83, 127−136 (1989). | PubMed | ChemPort |
29.	Vilaró, S., Llobera, M., Bengtsson-Olivecrona, G. & Olivecrona, T. Biochem. J. 249, 549−556 (1988). | PubMed |
30.	Vilaró, S., Ramírez, I., Bengtsson-Olivecrona, G., Olivecrona, T. & Llobera, M. Biochim. biophys. Acta. 259, 106−117 (1988).
31.	Weibel, E. R. Stereological Methods Vol. 1 Practical Methods for Biological Morphometry (Academic. London, 1980).