Increased muscle glucose uptake in response to chronic glyburide treatment is not related to changes in glucose transporter (GLUT4) protein.
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. A dietary induced insulin resistant rat model (4 wk of high-fat, high-sucrose feeding) was given glyburide (2 mg/kg/day) for 10 days and glucose uptake was measured in a perfused hindquarter preparation. 3. Protein levels of the GLUT4 glucose transporter were determined by Western analysis. 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. Glucose uptake was approx doubled in basal state (0 insulin) in response to glyburide (2.8 +/- 0.4 vs 1.7 +/- 0.2 mumol/g per hr). 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 mumol/g per hr). 7. Western analysis revealed no significant effect of glyburide on the GLUT4 protein level in skeletal muscle. 8. These results suggest that glyburide alters glucose uptake through some mechanism other than alterations in the level of the GLUT4 glucose transporter protein.
Kern
M
M
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, NC 27858.
Loomis
T A
TA
Tapscott
E B
EB
Dohm
G L
GL
D000818:Animals; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D005905:Glyburide / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009132:Muscles / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D005947:Glucose; D005905:Glyburide