title: Adult pancreatic islets require differential pax6 gene dosage.
abstract: Pax6, a paired homeodomain transcription factor, plays crucial roles in morphogenesis of eye, central nervous system, and pancreatic islets. Recently, heterozygosity for pax6 mutation has been reported in some individuals with glucose intolerance and aniridia. To investigate the role of pax6 for pancreatic islet function, we examined the pancreatic phenotype of small eye rat strain (rSey(2)) with a point mutation in the pax6 locus resulting in truncated PAX6 proteins. Analyses of the insulin secretory profile of heterozygous rSey(2)/+ revealed that insulin secretion is significantly increased in response to membrane-depolarizing stimuli such as arginine, tolbutamide, and KCl. The processes of insulin granule exocytosis were suggested to be enhanced in rSey(2)/+. On the other hand, pancreatic insulin and glucagon content and islet architecture in rSey(2)/+ showed no significant differences compared to wild-type. These findings indicate differential requirements for pax6 gene dosage in displaying function and maintaining architecture of adult pancreatic islets.
authors.affiliation: Department of Diabetes and Clinical Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hamasaki
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurose
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ban
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nagashima
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Shimpei
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Dai
authors.initials: D
authors.lastname: Shimono
authors.forename: Michio
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Seino
authors.forename: Nobuya
authors.initials: N
authors.lastname: Inagaki
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D018628:Gene Dosage / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605733:Pax6 protein, rat; D012097:Repressor Proteins; D005947:Glucose