GLUCOSE-INDUCED AND PHORBOL ESTER-INDUCED INSULIN-SECRETION IN HUMAN INSULINOMA CELLS - ASSOCIATION WITH PROTEIN-KINASE-C ACTIVATION

This study examined the effect of glucose and 12-O-tetradecanoylphorbo l-13-acetate (TPA) on insulin secretion in isolated human insulinoma c ells. In addition, we analyzed conventional PKC alpha and beta activat ion in the membrane fractions, respectively. Treatment with 5 mM and 2 0 mM glucose for 5 min and 20 min resulted in 6 similar to 7-fold incr eases in insulin secretion, and treatment with 1 mu M TPA for 5 min al so resulted in 3-fold increases in insulin secretion from the basal le vel. Immunoblot analysis of membrane fractions showed increases in PKC alpha and beta immunoreactivities after treatment with 5 mM, 20 mM gl ucose and 1 mu M TPA. Translocations of PKC alpha after treatment with glucose and TPA were greater than those of PKC beta in membrane fract ions. These results suggest that TPA independently provokes insulin se cretion via PKC activation and that PKC alpha and beta activation may be involved in insulin secretion in human insulinoma cells.