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

45 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume286
Issue number1 49-1
StatePublished - Jan 2004
Externally publishedYes

Fingerprint

Phosphorylation
Muscle
Hexokinase
Glucose
Muscles
Fasting
Quadriceps Muscle
Exercise equipment
Jugular Veins
Ambulatory Surgical Procedures
Carotid Arteries
Nonesterified Fatty Acids
Surgery
Blood
Sampling

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Distributed control of glucose uptake by working muscles of conscious mice : Roles of transport and phosphorylation. / Fueger, Patrick T.; Bracy, Deanna P.; Malabanan, Carlo M.; Pencek, R. Richard; Wasserman, David H.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 286, No. 1 49-1, 01.2004.

Research output: Contribution to journalArticle

Fueger, Patrick T. ; Bracy, Deanna P. ; Malabanan, Carlo M. ; Pencek, R. Richard ; Wasserman, David H. / Distributed control of glucose uptake by working muscles of conscious mice : Roles of transport and phosphorylation. In: American Journal of Physiology - Endocrinology and Metabolism. 2004 ; Vol. 286, No. 1 49-1.
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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.",
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