Inhibitory effect of sulfonylureas on protein phosphatase activity in rat pancreatic islets |
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Authors: | J. J. Gagliardino J. P. F. C. Rossi M. E. García |
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Affiliation: | (1) CENEXA, Centre of Experimental and Applied Endocrinology (UNLP-CONICET), Facultad de Ciencias Médicas, Calles 60 y 120, (1900) La Plata, Argentina, AR;(2) IQUIFIB, Institute of Chemistry and Biological Physicochemistry (UBA-CONICET), Buenos Aires, Argentina, AR |
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Abstract: | We have measured protein phosphatase (PP) activity in crude homogenates as well as in the total 105,000×g supernatant and precipitate fractions from normal rat pancreatic islets. On the basis of the inhibition produced by either 1 nM or 1 µM okadaic acid, both PP1 and PP2A activity were present in crude islet homogenates in equivalent proportions (53% and 47%, respectively); PP1 was the main activity present in the precipitate, whereas in the supernatant it was PP2A. Tolbutamide, glybenclamide and glyclazide significantly decreased PP activity in islet 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 KATP channel, and its EC50 on insulin release. These data indicate that PPs play a role in the control of insulin secretion and suggest a further possible target for sulfonylureas within their overall action as insulin secretagogues. |
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Keywords: | Protein phosphatase Sulfonylurea Protein phosphorylation Intracellular signals |
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