EFFECTS OF SODIUM-BUTYRATE ON GLUCOSE-TRANSPORTER AND GLUCOSE-PHOSPHORYLATING ENZYME GENE-EXPRESSION IN RINM5F INSULINOMA CELLS

RINm5F insulinoma cells show a defective physiological insulin secreto ry response to glucose stimulation. The short chain carbonic acid sodi um butyrate induced a growth arrest during a 72-h tissue culture perio d. In contrast to control RINm5F cells, 2 mM glucose increased insulin secretion by more than 70% in these sodium butyrate-treated cells (1 mM) without any further increase of the secretory rate between 2 and 2 0 mM glucose. This effect of sodium butyrate on insulin secretion was assessed in comparison with its effect on gene expression of the GLUT1 and GLUT2 glucose transporter, hexokinase type I and type II, glucoki nase and insulin. Sodium butyrate at a 1 mM concentration decreased GL UT1 gene expression by nearly 50%, but did not induce gene expression of the low-affinity GLUT1 glucose transporter above the detection limi t. Furthermore, sodium butyrate increased glucokinase gene expression by more than 50% and hexokinase type II gene expression by more than 1 00%, while insulin gene expression was increased only by 24%. Hexokina se type II enzyme activity was increased by more than 100% without a c oncomitant significant change of the glucokinase enzyme activity. Sodi um butyrate (2 mM) caused effects comparable with those of 1 mM sodium butyrate. Thus the improved insulin secretory responsiveness of RINm5 F insulinoma cells after sodium butyrate treatment at low non-physiolo gical millimolar glucose concentrations can be interpreted as a result of an increased hexokinase-mediated metabolic flux rate through the g lycolytic chain.