Increased muscle glucose uptake in response to chronic glyburide treatment is not related to changes in glucose transporter (GLUT4) protein |
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| Institution: | 1. Center for Spatial Information Science, The University of Tokyo 5-1-5 Kashiwanoha, Kashiwa-shi, Chiba 277-8568, Japan;2. Future Energy Center, Malardalen University, 721 23 Vasteras, Sweden;3. State Key Laboratory of New Energy Power Systems, North China Electric Power University, 102206 Beijing, China;4. SUSTech-UTokyo Joint Research Center on Super Smart City, Department of Computer Science and Engineering, Southern University of Science and Technology(SUSTech), Shenzhen, China;1. Department of Pediatrics, McGill University, Montreal, Quebec, Canada;2. Divisions of Infectious Diseases and Medical Microbiology, McGill University, Montreal, Quebec, Canada;3. Directorate of Professional Services, McGill University Health Centre, Montreal, Quebec, Canada;4. Nursing Directorate, Montreal Children''s Hospital, McGill University Health Centre, Montreal, Quebec, Canada |
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| Abstract: | - 1.1. The mechanism of action of glyburide (a sulfonylurea) on muscle has been investigated by measuring glucose uptake and glucose transporter (GLUT4) protein levels after chronic glyburide treatment.
- 2.2. A dietary induced insulin resistant rat model (4 wk of high-fat, high-sucrose feeding) was given glyburide (2mg/kg/day) for 10 days and glucose uptake was measured in a perfused hindquarter preparation.
- 3.3. Protein levels of the GLUT4 glucose transporter were determined by Western analysis.
- 4.4. After 7 days of treatment, rats fed glyburide had lower blood glucose concentrations 2 hr (72 ± 5 vs 103 ± 12 mg/dl) and 24 hr (97 ± 7 vs 123 ± 7 mg/dl) after glyburide administration with no difference in serum insulin levels compared to vehicle treated animals.
- 5.5. Glucose uptake was approx doubled in basal state (0 insulin) in response to glyburide (2.8 + 0.4 vs 1.7 ± 0.2μ mol/g per hr).
- 6.6. Maximal insulin (100 nM) stimulated glucose uptake tended to be higher in the glyburide treated group, but did not reach statistical significance (8.0 ± 0.7 vs 7.0 ± 0.6 μmol/g per hr).
- 7.7. Western analysis revealed no significant effect of glyburide on the GLUT4 protein level in skeletal muscle.
- 8.8. These results suggest that glyburide alters glucose uptake through some mechanism other than alterations in the level of the GLUT4 glucose transporter protein.
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