Distributed control of glucose uptake by working muscles of conscious mice: roles of transport and phosphorylation
| Autor: | Deanna P. Bracy, R. Richard Pencek, Patrick T. Fueger, David H. Wasserman, Carlo M. Malabanan |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Consciousness Monosaccharide Transport Proteins Physiology Ratón Endocrinology Diabetes and Metabolism Transgene Glucose uptake Muscle Proteins Mice Inbred Strains Mice Transgenic Biology Mice chemistry.chemical_compound Hexokinase Physical Conditioning Animal Physiology (medical) Internal medicine Hexokinase II medicine Animals Phosphorylation Muscle Skeletal chemistry.chemical_classification Glucose Transporter Type 4 Mice Inbred C57BL Glucose Endocrinology Enzyme chemistry biology.protein Female GLUT4 |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 286:E77-E84 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00309.2003 |
| Popis: | Muscle glucose uptake (MGU) is determined by glucose delivery, transport, and phosphorylation. C57Bl/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 Rgby 230 and 166% in the gastrocnemius and superficial vastus lateralis (SVL) muscles under sedentary conditions. GLUT4 overexpression was not able to augment exercise-stimulated Rgor Kg. Whereas HK II overexpression had no effect on fasting glycemia (170 ± 6 mg/dl) or sedentary Rg, it increased exercise-stimulated Rgby 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 Rgcompared 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. |
| Databáze: | OpenAIRE |
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