title: Involvement of novel protein kinase C isoforms in carbachol-stimulated insulin secretion from rat pancreatic islets.
abstract: The roles of protein kinase C (PKC) isoforms in cholinergic potentiation of glucose-induced insulin secretion were investigated in rat pancreatic islets. Western-blot analysis showed the presence of PKC-alpha, betaII, delta, epsilon, eta, and zeta, but not PKC-betaI, gamma, or iota, in the islets. Carbachol (CCh) caused translocations of PKC-alpha, betaII, delta, and epsilon from the cytosol to the plasma membrane. CCh facilitated 7-mM glucose-induced insulin secretion from isolated rat islets. The CCh-stimulated insulin secretion was significantly suppressed by the generic PKC inhibitor chelerythrine. In contrast, Go 6976, an inhibitor of conventional PKC isoforms, had no effect on the insulin secretion stimulated by CCh, although it significantly inhibited that induced by phorbol 12-myristate 13-acetate. These results suggest that the novel PKC isoforms activated by CCh, i.e., PKC-delta and/or epsilon, participate in the stimulatory effect of CCh on insulin secretion.
authors.affiliation: Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka-City, Shizuoka 422-8526, Japan. ishikat@u-shizuoka-ken.ac.jp
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Eri
authors.initials: E
authors.lastname: Iwasaki
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Kanatani
authors.forename: Fumi
authors.initials: F
authors.lastname: Sugino
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kaneko
authors.forename: Kazuo
authors.initials: K
authors.lastname: Obara
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007527:Isoenzymes; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D007328:Insulin; D007527:Isoenzymes; D002217:Carbachol; D011493:Protein Kinase C