GLUCOSE-METABOLISM AND INSULIN RELEASE IN MOUSE BETA-HC9 CELLS, AS MODEL FOR WILD-TYPE PANCREATIC BETA-CELLS

Glucose metabolism and its relationship with glucose-induced insulin r elease were studied in beta HC9 and beta TC3 cells to identify and cha racterize key factors controlling the intermediary metabolism of gluco se and glucose-induced insulin release. The beta HC9 cell line, derive d from pancreatic islets with beta-cell hyperplasia, is characterized by a normal concentration-dependency curve for glucose-stimulated insu lin release, whereas the beta TC3 cell line, derived from pancreatic b eta-cell tumors, shows a marked leftward shift of this curve. Maximum velocity and the Michaelis-Menten constant of glucose uptake in beta H C9 and beta TC3 cells were similar, even though GLUT-2 expression in t hese two cell lines differed. In both cell lines, the kinetic characte ristics of glucose usage, glucose oxidation, and glucose-induced oxyge n consumption were similar to those of glucose phosphorylation, indica ting that the kinetics of glucose metabolism from the glucose phosphor ylation step in the cytosol to the mitochrondrial process of oxidative phosphorylation are determined by the glucose-phosphorylating enzyme, that is, by glucokinase in beta HC9 cells and by hexokinase in beta T C3 cells. Thus beta HC9 cells provide an opportunity for the quantitat ive analysis of glucose metabolism, the associated generation of coupl ing factors, and other essential beta-cell functions involved in gluco se sensing and insulin secretion.