Abstract
A recent report indicates that the Na+-D-glucose cotransporter SGLT1 is present in capillaries of skeletal muscle and is required for insulin-mediated glucose uptake in myocytes. This result is based on the complete inhibition of insulin-mediated muscle glucose uptake by phlorizin, an inhibitor of SGLT1. Using the pump-perfused rat hind limb, we measured glucose uptake, lactate efflux, and radioactive 2-deoxyglucose uptake into individual muscles with saline (control), phlorizin, insulin, and insulin plus phlorizin, as well as with saline and insulin using normal and low Na+ perfusion buffer. Insulin-mediated glucose uptake was not inhibited after correction for phlorizin interference in the glucose assay. Lactate efflux and 2-deoxyglucose uptake by individual muscles were unaffected by phlorizin. Low Na+ buffer did not affect insulin-mediated glucose uptake, lactate efflux, or 2-deoxyglucose uptake. We conclude that endothelial SGLT1 exerts no barrier for glucose delivery to myocytes.
Key words
Glucose transport - Na+-D-glucose cotransporter - phlorizin - muscle - capillary
References
-
1
Wright E M, Hager K M, Turk E.
Sodium cotransport proteins.
Curr Opin Cell Biol.
1992;
4
696-702
-
2
Elfeber K, Stumpel F, Gorboulev V, Mattig S, Deussen A, Kaissling B, Keopsell H.
Na+-D-glucose cotransporter in muscle capillaries increases glucose permeability.
Biochem Biophys Res Commun..
2004;
314
301-305
-
3
Loike J D, Hickman S, Kuang K, Xu M, Cao L, Vera J C, Silverstein S C, Fischbarg J.
Sodium-glucose cotransporters display sodium- and phlorizin-dependent water permeability.
Am J Physiol.
1996;
271
C1774-C1779
-
4
Ruderman N B, Houghton C R, Hems R.
Evaluation of the isolated perfused rat hindquarter for the study of muscle metabolism.
Biochem J.
1971;
124
639-651
-
5
Colquhoun E Q, Hettiarachchi M, Ye J M, Richter E A, Hniat A J, Rattigan S, Clark M G.
Vasopressin and angiotensin II stimulate oxygen uptake in the perfused rat hindlimb.
Life Sci.
1988;
43
1747-1754
-
6
Clark M G, Colquhoun E Q, Rattigan S, Dora K A, Eldershaw T P, Hall J L, Ye J.
Vascular and endocrine control of muscle metabolism.
Am J Physiol.
1995;
268
E797-E812
-
7
Dora K A, Richards S M, Rattigan S, Colquhoun E Q, Clark M G.
Serotonin and norepinephrine vasoconstriction in rat hindlimb have different oxygen requirements.
Am J Physiol.
1992;
262
H698-H703
-
8
Kraegen E W, James D E, Jenkins A B, Chisholm D J.
Dose-response curves for in vivo insulin sensitivity in individual tissues in rats.
Am J Physiol.
1985;
248
E353-E362
-
9
James D E, Jenkins A B, Kraegen E W.
Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats.
Am J Physiol.
1985;
248
E567-E574
-
10
Miller J H, Mullin J M, McAvoy E, Kleinzeller A.
Polarity of transport of 2-deoxy-D-glucose and D-glucose by cultured renal epithelia (LLC-PK1).
Biochim Biophys Acta.
1992;
1110
209-217
-
11
Kasahara T, Kasahara M.
Characterization of rat GLUT4 glucose transporter expressed in the yeast Saccharomyces cerevisiae: comparison with GLUT1 glucose transporter.
Biochim Biophys Acta.
1997;
1324
111-119
-
12
Vock R, Weibel E R, Hoppeler H, Ordway G, Weber J M, Taylor C R.
Design of the oxygen and substrate pathways. V. Structural basis of vascular substrate supply to muscle cells.
J Exp Biol.
1996;
199
1675-1688
C. M. Kolka
Dept of Biochemistry · Medical School · Private Bag 58 · University of Tasmania
Hobart · TAS 7001 · Australia
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