D-glucose metabolism in cross-linked pancreatic islets

D-glucose metabolism was investigated in pancreatic islets that underwent cross-linking of intracellular proteins by dimethyl suberimidate. Both the utilization of D-[5-3H]glucose and oxidation of D-[U-14C]glucose were much more severely affected at high (16.7 mM) than at low (2.8 mM) concentration of the hexose, when comparing cross-linked to control islets. The preferential stimulation of D-[U-14C]glucose oxidation relative to D-[5-3H]glucose utilization, resulting from an increase in hexose concentration, was not abolished, however, in cross-linked islets. Likewise, the activation of phosphofructokinase in glucose-stimulated islets did not appear to be impaired in cross-linked islets, the islet content in tritiated acidic metabolites generated from D-[5-3H]glucose failing to be increased in cross-linked islets. It is proposed, therefore, that the impaired responsiveness of cross-linked islets to a rise in D-glucose concentration might be attributable to an altered regulation of glucokinase, as possibly resulting from a missing interaction of the enzyme with GLUT-2.