Metabolism of d-glucose and its pentaacetate ester in muscles and pancreatic islets of GLUT4 null mice.
The metabolism of d-glucose and its pentaacetate ester was investigated in GLUT4 null mice and control C57Bl6/CBA mice. The incorporation of d-[U-(14)C]glucose (1.7 mM) into glycogen of diaphragm, soleus, and extensor digitorium longus muscles averaged, in the GLUT4 null mice, only 34 +/- 7% of the mean corresponding control values. The utilization of d-[5-(3)H]glucose and conversion of d-[U-(14)C]glucose to (14)CO(2) and radioactive acidic metabolites or amino acids were little affected, however, in the muscles from GLUT4 null mice. Likewise, under steady-state conditions, the intracellular pool of 6-deoxy-6-iodo-d-glucose (10 microM) was not significantly different in muscles from GLUT4 null and control mice. The incorporation of d-[U-(14)C]glucose pentaacetate (1.7 mM) into glycogen and utilization of d-[5-(3)H]glucose pentaacetate were also not significantly different in muscles from GLUT4 null and control animals. They were about 10-30 times lower than the corresponding values found with the unesterified hexose. In pancreatic islets, however, the metabolism of d-glucose pentaacetate was not lower than that of unesterified d-glucose. Moreover, the utilization of d-[5-(3)H]glucose and catabolism of d-[U-(14)C]glucose were significantly higher in the islets from GLUT4 null mice than in those from control animals. These findings indicate that the defect of d-glucose metabolism in GLUT4 null mice occurs in muscles but not in pancreatic islets, affects preferentially glycogen synthesis rather than glycolysis, and can be bypassed by using the pentaacetate ester of the hexose. The present data also reveal a striking difference between muscles and islets when comparing the metabolism of d-glucose to that of its ester.
Ladrière
L
L
Laboratory of Experimental Medicine, Brussels Free University, Brussels, Belgium.
Charron
M J
MJ
Malaisse
W J
WJ
D000818:Animals; D001692:Biological Transport; D005947:Glucose / Q000031:analogs & derivatives* / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D051379:Mice; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000172:deficiency / Q000235:genetics*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism*
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; C105128:glucose pentaacetate; D005947:Glucose