Inhibitory effect of sulfonylureas on protein phosphatases activity in rat pancreatic islets

38. GAGLIARDINO, J.J., GARCÍA, M.E. AND ROSSI, J.P.F.C.

ACTA DIABETOLOGICA.

SPRINGER

Lugar: Berlin; Año: 1997 vol. 34 p. 6 - 9

0940-5429

Abstract We have measured protein phosphatase (PP) activityin crude homogenates as well as in the total105,000´g supernatant and precipitate fractions from normalrat pancreatic islets. On the basis of the inhibition producedby either 1 nM or 1 mM okadaic acid, both PP1 andPP2A activity were present in crude islet homogenates inequivalent proportions (53% and 47%, respectively); PP1was the main activity present in the precipitate, whereas inthe supernatant it was PP2A. Tolbutamide, glybenclamideand glyclazide significantly decreased PP activity in islethomogenates in a dose-dependent manner, with a Ki0.5value that in the case of glybenclamide correlated with itsKd for binding site, its EC50 on KATP channel, and its EC50on insulin release. These data indicate that PPs play a rolein the control of insulin secretion and suggest a further possibletarget for sulfonylureas within their overall action asinsulin secretagogues.