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
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
收藏
页码:36 / 45
页数:10
相关论文
共 54 条
[11]   Synaptotagmin III/VII isoforms mediate Ca2+-induced insulin secretion in pancreatic islet β-cells [J].
Gao, ZY ;
Reavey-Cantwell, J ;
Young, RA ;
Jegier, P ;
Wolf, BA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (46) :36079-36085
[12]   Synaptotagmins bind calcium to release insulin [J].
Gauthier, Benoit R. ;
Wollheim, Claes B. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2008, 295 (06) :E1279-E1286
[13]   Section 1:: Insulin release:: Some molecular requisites -: Molecular determinants of regulated exocytosis [J].
Gerber, SH ;
Südhof, TC .
DIABETES, 2002, 51 :S3-S11
[14]   Is reduced first-phase : Insulin release the earliest detectable abnormality in individuals destined to develop type 2 diabetes? [J].
Gerich, JE .
DIABETES, 2002, 51 :S117-S121
[15]  
Ghanaat-Pour H., 2011, METABOLOMICS, V1, P1
[16]   Gene expression regulated by pioglitazone and exenatide in normal and diabetic rat islets exposed to lipotoxicity [J].
Ghanaat-Pour, Hamedeh ;
Sjoeholm, Ake .
DIABETES-METABOLISM RESEARCH AND REVIEWS, 2009, 25 (02) :163-184
[17]   Distinct roles of the C2A and the C2B domain of the vesicular Ca2+ sensor synaptotagmin 9 in endocrine β-cells [J].
Grise, Florence ;
Taib, Nada ;
Monterrat, Carole ;
Lagree, Valerie ;
Lang, Jochen .
BIOCHEMICAL JOURNAL, 2007, 403 (03) :483-492
[18]   Diabetes mellitus, a microRNA-related disease? [J].
Guay, Claudiane ;
Roggli, Elodie ;
Nesca, Valeria ;
Jacovetti, Cecile ;
Regazzi, Romano .
TRANSLATIONAL RESEARCH, 2011, 157 (04) :253-264
[19]   Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice [J].
Gustavsson, Natalia ;
Lao, Ye ;
Maximov, Anton ;
Chuang, Jen-Chieh ;
Kostromina, Elena ;
Repa, Joyce J. ;
Li, Cai ;
Radda, George K. ;
Suedhof, Thomas C. ;
Han, Weiping .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (10) :3992-3997
[20]  
Gut A, 2001, J CELL SCI, V114, P1709