The anomeric specificity of thé wild-type recombinant forms of human liver and B-cell glucokinase was investigated using radioactive anomers of D-glucose as tracers. With D-glucose at anomeric equilibrium and at 30°C, thé maximal velocity, Hill number, and K, amounted, respectively, to 16 /.unol min"1 mg"1,1.8 and 6.9 mM in thé case of liver glucokinase, and 7. The anomeric specificity of liver and pancreatic islet glucokinase was examined by several investigators (1-5). Interest in this matter is motivated inter alla by thé knowledge that, under physiological conditions, a-Dglucose is a more potent insulin secretagog than /3-Dglucose (6-10). Because of thé key rôle played by glucokinase in thé régulation of D-glucose metabolism in islet insulin-producing cells (11), thé question was raised whether thé anomeric specificity of B-cell glucokinase may indeed account for thé higher insulinotropic capacity of a-D-glucose (4, 5). Moreover, in noninsulin-dependent diabètes mellitus, thé préférence of thé B-cell secretory response for a-relative to /3-Dglucose is often decreased and may even be inverted (12-16). Although such a perturbation, which can be reproduced in normal rats through sustained hyperglycemia caused by either thé administration of diazoxide (17) or partial pancreatectomy (18), appears usually attributable to glycogen accumulation in thé pancreatic islet cells (19), a mutation of thé glucokinase gène resulting in an altered anomeric behavior of thé enzyme, was also considered as a possible and exceptional cause for thé anomeric malaise in insulin sécré-tion (20).In intact B-cells, however, thé phosphorylation of D-glucose is not ruled solely by thé cytosolic concentration of thé hexose and thé intrinsic properties of glucokinase and hexokinase. It can also be affected by a number of other factors, such as thé concentration of ATP and D-glucose 6-phosphate (21, 22), thé binding of thé hexokinase isoenzymes to mitochondrial porin (23-25), thé modulation of glucokinase activity by its reg-126
