Identification and significance of glucokinase in transplantable insulinomas

Glucose 6-phosphotransferases were investigated in two transplantable rat insulinoma tumor lines. Homogenates of tumors contained glucose phosphorylating activities of both high (e.g. supernatant K(m) = 0.060 mM and pellet K(m) = 0.077 mM) and low (K(m) = 7.6 mM) affinities for glucose. Chromatography of supernatants (105,000 x g) of insulinomas on DEAE-Cibacron Blue F3GA agarose evidenced glucose 6-phosphotransferase activity which eluted similarly to glucokinase from rat liver. Kinetic studies of insulinoma glucokinase also indicated similarity with liver glucokinase, i.e. cooperative rate dependence on glucose concentration and comparable K(m) values for glucose, and it did not phosphorylate N-acetylglucosamine. These characteristics of glucose 6-phosphotransferase in insulinomas are similar to those of the enzyme found in islets of Langerhans. Since glucokinase is thought to serve as glucose sensor of insulin secretory pancreatic β-cells, these transplantable insulinomas offer great promise for biochemical and biophysical studies of the nature of glucose-induced insulin release.