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 C57B16/CBA mice. The incorporation of D-[U-C-14 ]glucose (1.7 mM) into glycogen of diaphragm, soleus, and extensor digitori um longus muscles averaged, in the GLUT4 null mice, only 34 +/- 7% of the m ean corresponding control values. The utilization of D-[5-H-3]glucose and c onversion of D-[U-C-14]glucose to (CO2)-C-14 and radioactive acidic metabol ites or amino acids mere little affected, however, in the muscles from GLUT 4 null mice. Likewise, under steady-state conditions, the intracellular poo l of 6-deoxy-6-iodo-D-glucose (10 mu M) was not significantly different in muscles from GLUT4 null and control mice. The incorporation of D-[U-C-14]gl ucose pentaacetate (1.7 mM) into glycogen and utilization of D-[5-H-3]gluco se pentaacetate were also not significantly different in muscles from GLUT4 null and control animals. They were about 10-30 times lower than the corre sponding values found with the unesterified hexose, In pancreatic islets, h owever, the metabolism of D-glucose pentaacetate was not lower than that of unesterified D-glucose, Moreover, the utilization of D-[5-H-3]glucose and catabolism of D-[U-C-14]glucose were significantly higher in the islets fro m GLUT4 null mice than in those from control animals. These findings indica te that the defect of D-glucose metabolism in GLUT4 null mice occurs in mus cles but not in pancreatic islets, affects preferentially glycogen synthesi s rather than glycolysis, and can be bypassed by using the pentaacetate est er of the hexose, The present data also reveal a striking difference betwee n muscles and islets when comparing the metabolism of D-glucose to that of its ester, (C) 1999 Academic Press.