title: Cellular mechanism of glyburide-induced insulin gene expression in isolated rat islets.
abstract: The cellular mechanism for the effects of glyburide on the synthesis and release of insulin and insulin gene expression in isolated islets was investigated. On incubation for 1 h, glyburide increased insulin release without affecting either the insulin content or the PPI mRNA level. H-7, an inhibitor of PKC, inhibited the glyburide-induced insulin release, while H-8, an inhibitor of cyclic nucleotide-dependent protein kinases, did not affect the glyburide-induced insulin release. On incubation for 20 h, glyburide increased insulin release and the PPI mRNA level, without affecting the insulin content. H-7 inhibited glyburide-induced insulin release and increased the PPI mRNA level. H-8 significantly inhibited both the glyburide-induced increase in insulin release and increase in PPI mRNA level. In conclusion, glyburide stimulated insulin release via a PKC-mediated pathway and increased the PPI mRNA level via cyclic nucleotide-dependent protein kinase(s).
authors.affiliation: Department of Geriatric Medicine, Osaka University Medical School, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Yamato
authors.forename: H
authors.initials: H
authors.lastname: Ikegami
authors.forename: Y
authors.initials: Y
authors.lastname: Tahara
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: T
authors.initials: T
authors.lastname: Cha
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Fujioka
authors.forename: Y
authors.initials: Y
authors.lastname: Noma
authors.forename: K
authors.initials: K
authors.lastname: Shima
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002478:Cells, Cultured; D015342:DNA Probes; D015870:Gene Expression / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology*; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011384:Proinsulin / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015342:DNA Probes; D007328:Insulin; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011498:Protein Precursors; D012333:RNA, Messenger; C013737:preproinsulin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D011384:Proinsulin; D011494:Protein Kinases; D011493:Protein Kinase C; D005905:Glyburide