Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes

被引：100

作者：

Andersson, Sofia A. ^{[1
]}

Olsson, Anders H. ^{[1
]}

Esguerra, Jonathan L. S. ^{[1
]}

Heimann, Emilia ^{[2
]}

Ladenvall, Claes ^{[1
]}

Edlund, Anna ^{[1
]}

Salehi, Albert ^{[1
]}

Taneera, Jalal ^{[1
]}

Degerman, Eva ^{[2
]}

Groop, Leif ^{[1
]}

Ling, Charlotte ^{[1
]}

Eliasson, Lena ^{[1
]}

机构：

[1] Lund Univ, Ctr Diabet, Dept Clin Sci Malmo, S-20502 Malmo, Sweden

[2] Lund Univ, Dept Expt Med Sci, Biomed Ctr, S-20502 Malmo, Sweden

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2012年 / 364卷 / 1-2期

基金：

瑞典研究理事会;

关键词：

Type; 2; diabetes; Islet; Beta-cell; Exocytosis; SYT; GWAS; BETA-CELLS; CA2+ CHANNELS; RAT ISLETS; MECHANISMS; 1ST-PHASE; VARIANTS; PROTEIN; SYNTAXIN-1A; ISOFORMS; GRANULES;

D O I：

10.1016/j.mce.2012.08.009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Reduced insulin release has been linked to defect exocytosis in beta-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (chi(2) = 13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human 120 islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

引用

页码：36 / 45

页数：10

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