In vitro expression of NGN3 identifies RAB3B as the predominant Ras-associated GTP-binding protein 3 family member in human islets

被引:17
作者
Hanley, Karen Piper [1 ]
Hearn, Tom [2 ]
Berry, Andrew [1 ]
Carvell, Melanie J. [3 ]
Patch, Ann-Marie [4 ]
Williams, Louise J. [2 ]
Sugden, Sarah A. [1 ]
Wilson, David I. [2 ]
Ellard, Sian [4 ]
Hanley, Neil A. [1 ]
机构
[1] Univ Manchester, Manchester Acad Hlth Sci Ctr, Endocrinol & Diabet Grp, Manchester M13 9PT, Lancs, England
[2] Univ Southampton, Div Human Genet, Southampton SO16 6YD, Hants, England
[3] Kings Coll London, Beta Cell Dev & Funct Grp, London SE1 1UL, England
[4] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England
基金
英国惠康基金;
关键词
PANCREATIC BETA-CELLS; CONGENITAL MALABSORPTIVE DIARRHEA; INSULIN-SECRETING CELLS; DIFFERENTIATION PROGRAM; GLUCOSE-INTOLERANCE; MUTANT NEUROGENIN-3; CA2+ SENSOR; GENE; EXOCYTOSIS; ENDOCRINE;
D O I
10.1677/JOE-10-0120
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 beta-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 beta-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. Journal of Endocrinology (2010) 207, 151-161
引用
收藏
页码:151 / 161
页数:11
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