title: Effects of the protein phosphatase inhibitors okadaic acid and calyculin A on insulin release from rat pancreatic islets.
abstract: The role of protein phosphatases in the regulation of insulin release from rat pancreatic islets was studied with protein phosphatase inhibitors, okadaic acid and calyculin A. Okadaic acid inhibited glucose- and glyceraldehyde-induced insulin release dose-dependently and also inhibited the potentiation of glucose-induced release either by adding forskolin, an activator of adenylate cyclase or by increasing K+ concentration to 25 mM. At a non-stimulatory concentration of 3 mM glucose, a high concentration (2 microM) of okadaic acid inhibited insulin release induced by high K+ or 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, but a low concentration (1 microM) of okadaic acid did not significantly inhibit TPA-induced insulin release. Calyculin A also inhibited glucose-induced insulin release, and the effect was greater than that of okadaic acid. The data suggest that protein phosphatases may play an important role in the regulation of insulin release.
authors.affiliation: Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tamagawa
authors.forename: A
authors.initials: A
authors.lastname: Iguchi
authors.forename: K
authors.initials: K
authors.lastname: Uemura
authors.forename: H
authors.initials: H
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Nonogaki
authors.forename: T
authors.initials: T
authors.lastname: Ishiguro
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
mesh_terms: D000818:Animals; D005576:Colforsin; D004305:Dose-Response Relationship, Drug; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005947:Glucose; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008387:Marine Toxins; D019319:Okadaic Acid; D010080:Oxazoles / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011188:Potassium; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate
chemical_list: D004988:Ethers, Cyclic; D007328:Insulin; D008387:Marine Toxins; D010080:Oxazoles; D005576:Colforsin; D019319:Okadaic Acid; C059041:calyculin A; D010749:Phosphoprotein Phosphatases; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium