Glibenclamide but not other sulphonylureas stimulates release of neuropeptide Y from perifused rat islets and hamster insulinoma cells

We have studied the effects of first and second generation sulphonylureas o n the release of insulin and neuropeptide tyrosine (NPY) fi-om hamster insu linoma tumour (HIT-T15) cells and isolated rat islets. In the presence of 5 .5 mmol/l glucose all sulphonylureas stimulated insulin release from the HI T cells (P<0.01 ANOVA, n greater than or equal to 4) but only glibenclamide (GLIB, 10 mu mol/l) stimulated the release of NPY (mean +/- S.E.M. control 11.1 +/- 1.3 vs GLIB 28.4 +/- 4.1 fmol/h per 10(6) cells, P<0001, n=16). I n isolated perifused rat islets both glibenclamide (10 mu mol/l) (control 3 .5 +/- 0.3 vs GLIB 6.3 +/- 0.2 fmol/min per islet, P<0.01, n=6) and tolbuta mide (50 mu mol/l) (control 4.7 +/- 0.1 vs TOLB 6.7 +/- 0.3 fmol/min per is let, P<0.01, n=6) enhanced glucose (8 mmol/l)-stimulated insulin release. H owever, only glibenclamide stimulated the release of NPY from the islets (c ontrol 3.4 +/- 0.8 vs GLIB 24.5 +/- 5 attomol/min per islet, P<0.01, n=6). Similar results were obtained in islets isolated from dexamethasone-treated rats. Glibenclamide treatment of HIT cells showed a prompt insulin release (10 min) while NPY secretion was slower (60 min), suggesting that internal ization of the sulphonylurea is required to stimulate NPY release. Glibencl amide, the most common oral therapeutic agent in type 2 diabetes mellitus, is associated with release of the autocrine insulin secretion inhibitor, NP Y.