INHIBITORY EFFECT OF SULFONYLUREAS ON PROTEIN PHOSPHATASE-ACTIVITY INRAT PANCREATIC-ISLETS

We have measured protein phosphatase (PP) activity in crude homogenate s as well as in the total 105,000xg supernatant and precipitate fracti ons from normal rat pancreatic islets. On the basis of the inhibition produced by either 1 nM or 1 mu M okadaic acid, both PP1 and PP(2)A ac tivity were present in crude islet homogenates in equivalent proportio ns (53% and 47%, respectively); PP1 was the main activity present in t he precipitate, whereas in the supernatant it was PP(2)A. Tolbutamide, glybenclamide and glyclazide significantly decreased PP activity in i slet homogenates in a dose-dependent manner, with a K-i0.5 value that in the case of glybenclamide correlated with its K-d for binding site, its EC50 on K-ATP channel, and its EC50 on insulin release. These dat a indicate that PPs play a role in the control of insulin secretion an d suggest a further possible target for sulfonylureas within their ove rall action as insulin secretagogues.