Characteristics of glucokinase of the Kirkman insulinoma.
It was investigated whether the well-known transplantable insulinoma of the hamster (the Kirkman tumor) contains glucokinase and if so, what its kinetic characteristics are, and whether its cellular levels might be regulated in a manner typical for islet tissue. The supernatant of tumor homogenates contained a low-affinity component (Km 9.7 mmol/L) of glucose phosphorylating activity, apparently glucokinase. Partially purified insulinoma glucokinase exhibited similar kinetic characteristics to liver glucokinase (Km for glucose 5.0 and 5.3 mmol/L, half-maximal saturation 6.9 and 6.3 mmol/L, Hill coefficient 1.63 and 1.62, Ki for mannoheptulose 0.9 and 0.6 mmol/L in hamster insulinoma glucokinase and hamster liver glucokinase, respectively). Insulinoma glucokinase activity was not affected by the age of the tumor. Tumor-bearing hamsters without further treatment stayed normoglycemic (172 +/- 9.5 mg/dL) for the duration of the experiment. Fasting caused hypoglycemia (49 +/- 5.0 mg/dL), and pretreatment with streptozotocin prior to tumor transplantation caused hyperglycemia (393 +/- 20.6 mg/dL) in the tumor-bearing hamsters. Blood glucose levels of the host hamsters did not affect the content of the insulinoma glucokinase (83 +/- 3.5 mU/g in hypoglycemic group, 88 +/- 9.0 mU/g in hyperglycemic group, and 86 +/- 3.5 mU/g in normoglycemic group). Thus, biosynthesis and degradation of insulinoma glucokinase does not seem to be regulated by glucose as found to be true for islet glucokinase. Since glucokinase is constitutively present, the stable transplantable Kirkman tumor could serve as a useful model for studying the pancreatic B-cell glycolysis system which is characterized by the presence of both hexokinase and glucokinase.
Shimizu
T
T
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104.
Matschinsky
F M
FM
D007516:Adenoma, Islet Cell / Q000201:enzymology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D006224:Cricetinae; D005941:Glucokinase / Q000032:analysis*; D006019:Glycolysis; D006593:Hexokinase / Q000032:analysis; D007340:Insulinoma / Q000201:enzymology*; D007515:Islets of Langerhans / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008647:Mesocricetus; D010190:Pancreatic Neoplasms / Q000201:enzymology*
D001786:Blood Glucose; D006593:Hexokinase; D005941:Glucokinase