Endothelial Na⁺-D-glucose Cotransporter: No Role in Insulin-mediated Glucose Uptake

 

 Buy Article Permissions and Reprints

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.

References

• 1 Wright E M, Hager K M, Turk E. Sodium cotransport proteins.  Curr Opin Cell Biol. 1992;  4 696-702
  CrossrefPubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  CrossrefPubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar
• 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
  PubMedGoogle Scholar

C. M. Kolka

Dept of Biochemistry · Medical School · Private Bag 58 · University of Tasmania

Hobart · TAS 7001 · Australia

Phone: +61 (3) 62 26 27 01

Fax: +61 (3) 62 26 27 03

Email: ckolka@utas.edu.au