Distributed control of glucose uptake by working muscles of conscious mice: Roles of transport and phosphorylation

Patrick T. Fueger, Deanna P. Bracy, Carlo M. Malabanan, R. Richard Pencek, David H. Wasserman

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Muscle glucose uptake (MGU) is determined by glucose delivery, transport, and phosphorylation. C57B1/6J mice overexpressing GLUT4, hexokinase II (HK II), or both were used to determine the barriers to MGU. A carotid artery and jugular vein were catheterized for arterial blood sampling and venous infusions. Experiments were conducted in conscious mice ∼7 days after surgery. 2-Deoxy-[3H]glucose was administered during rest or treadmill exercise to calculate glucose concentration-dependent (Rg) and -independent (Kg) indexes of MGU. Compared with wild-type controls, GLUT4-overexpressing mice had lowered fasting glycemia (165 ± 6 vs. 115 ± 6 mg/dl) and increased Rg by 230 and 166% in the gastrocnemius and superficial vastus lateralis (SVL) muscles under sedentary conditions. GLUT4 overexpression was not able to augment exercise-stimulated Rg or Kg. Whereas HK II overexpression had no effect on fasting glycemia (170 ± 6 mg/dl) or sedentary Rg, it increased exercise-stimulated Rg by 82, 60, and 169% in soleus, gastrocnemius, and SVL muscles, respectively. Combined GLUT4 and HK II overexpression lowered fasting glycemia (106 ± 6 mg/dl), increased nonesterified fatty acids, and increased sedentary Rg. Combined GLUT4 and HK II overexpression did not enhance exercise-stimulated R g compared with HK II-overexpressing mice because of the reduced glucose concentration. GLUT4 combined with HK II overexpression resulted in a marked increase in exercise-stimulated Kg. In conclusion, control of MGU shifts from membrane transport at rest to phosphorylation during exercise. Glucose transport is not normally a significant barrier during exercise. However, when the phosphorylation barrier is lowered by HK II overexpression, glucose transport becomes a key site of control for regulating MGU during exercise.

Original languageEnglish (US)
Pages (from-to)E77-E84
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume286
Issue number1 49-1
DOIs
StatePublished - Jan 2004

Keywords

  • 2-deoxyglucose
  • Delivery
  • Exercise
  • Glucose transporter 4
  • Hexokinase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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