Insulin secretion and differential gene expression in glucose-responsive and -unresponsive MIN6 sublines

We have established two sublines derived from the insulin-secreting mouse p ancreatic beta-cell line MIN6, designated m9 and m14. m9 Cells exhibit gluc ose-induced insulin secretion in a concentration-dependent manner, whereas m14 cells respond poorly to glucose. In m14 cells, glucose consumption and lactate production are enhanced, and ATP production is largely through nono xidative pathways. Moreover, lactate dehydrogenase activity is increased, a nd hexokinase replaces glucokinase as a glucose-phosphorylating enzyme. The ATP-sensitive K+ channel activity and voltage-dependent calcium channel ac tivity in m14 cells are reduced, and the resting membrane potential is sign ificantly higher than in m9 cells. Thus, in contrast to m9, a model for bet a-cells with normal insulin response, m14 is a model for beta-cells with im paired glucose-induced insulin secretion. By mRNA differential display of t hese sublines, we found 10 genes to be expressed at markedly different leve ls. These newly established MIN6 cell sublines should be useful tools in th e analysis of the genetic and molecular basis of impaired glucose-induced i nsulin secretion.