title: In vitro expression of NGN3 identifies RAB3B as the predominant Ras-associated GTP-binding protein 3 family member in human islets.
abstract: Neurogenin 3 (NGN3) commits pancreatic progenitors to an islet cell fate. We have induced NGN3 expression and identified upregulation of the gene encoding the Ras-associated small molecular mass GTP-binding protein, RAB3B. RAB3B localised to the cytoplasm of human β-cells, both during the foetal period and post natally. Genes encoding alternative RAB3 proteins and RAB27A were unaltered by NGN3 expression and in human adult islets their transcripts were many fold less prevalent than those of RAB3B. The regulation of insulin exocytosis in rodent β-cells and responsiveness to incretins are reliant on Rab family members, notably Rab3a and Rab27a, but not Rab3b. Our results support an important inter-species difference in regulating insulin exocytosis where RAB3B is the most expressed isoform in human islets.
authors.affiliation: Endocrinology and Diabetes Group, Manchester Academic Health Science Centre, University of Manchester, A V Hill Building, Oxford Road, Manchester M13 9PT, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Piper Hanley
authors.forename: Tom
authors.initials: T
authors.lastname: Hearn
authors.forename: Andrew
authors.initials: A
authors.lastname: Berry
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Carvell
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Patch
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Williams
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Sugden
authors.forename: David I
authors.initials: DI
authors.lastname: Wilson
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hanley
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005333:Fetus; D005786:Gene Expression Regulation / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000075745:rab27 GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005934:Glucagon; D007328:Insulin; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012313:RNA; D020691:rab GTP-Binding Proteins; D000075745:rab27 GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; C498695:NEUROG3 protein, human; C492131:RAB3B protein, human; C066694:RAB27A protein, human
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