THE EFFECT OF FRUCTOSE METABOLISM ON THE ACCUMULATION OF INOSITOL PHOSPHATES IN RAT PANCREATIC-ISLETS

The mechanism by which glucose recognition of B cells results in the r elease of inositol 1,4,5-trisphosphate is not known at present. In pan creatic islets, fructose shares a common metabolic pathway with glucos e from the second step of glycolysis and can augment insulin secretion at stimulatory glucose levels. To evaluate the impact of glycolysis o n the release of inositol 1,4,5-trisphosphate, we studied the effect o f glucose and fructose metabolism on insulin secretion and the activat ion of inositol-specific phospholipase C, using collagenase digested r at pancreatic islets incorporated with H-3-labelled myo-inositol. Inos itol phosphates, generated by the cleavage of phosphatidyl inositol by inositol phospholipase C, were analysed using fast protein liquid chr omatography. The islets were exposed to 3.3, 5.5 and 12 mmol l(-1) glu cose for 45 min in the absence or presence of 10, 20 or 30 mmol l(-1) fructose, and the amount of insulin released into the medium was measu red. Intracellular inositol phosphate accumulation was measured under the same glucose concentrations with 0, 10 and 30 mmol l(-1) fructose. As expected, fructose alone had no insulinotropic effect, but potenti ated the glucose-induced (5.5 and 12 mmol l(-1)) insulin secretion at concentrations of 10-30 mmol l(-1). Glucose (12 vs. 3.3 mmol l(-1)) si gnificantly increased both intracellular content of inositol 1,4,5-tri sphosphate, as well as its metabolite inositol 1,3,4-trisphosphate. Fr uctose, however, had no potentiating effects on the accumulation of in ositol phosphates. It is therefore supposed that glucose does not acti vate inositol-specific phospholipase C via the glycolysis. Further, si nce fructose did not activate inositol-specific phospholipase C, this stimulation is likely to be induced by glucose as such.