RETRACTED: The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes(Retracted article. See vol. 66, pg.1426, 2017)

被引:30
作者
Bostrom, Pontus [1 ]
Andersson, Linda [1 ]
Vind, Birgitte [2 ]
Haversen, Liliana [1 ]
Rutberg, Mikael [1 ]
Wickstrom, Ylva [1 ]
Larsson, Erik [1 ]
Jansson, Per-Anders [1 ]
Svensson, Maria K. [1 ]
Branemark, Richard [3 ]
Ling, Charlotte [4 ]
Beck-Nielsen, Henning [2 ]
Boren, Jan [1 ]
Hojlund, Kurt [2 ]
Olofsson, Sven-Olof [1 ]
机构
[1] Sahlgrens Univ Hosp, Sahlgrenska Ctr Cardiovasc & Metab Res, Wallenberg Lab, Gothenburg, Sweden
[2] Odense Univ Hosp, Diabet Res Ctr, Dept Endocrinol, DK-5000 Odense, Denmark
[3] Sahlgrens Univ Hosp, Dept Orthoped Surg, Gothenburg, Sweden
[4] Lund Univ, Dept Clin Sci CRC, Malmo Univ Hosp, S-22100 Lund, Sweden
基金
瑞典研究理事会;
关键词
LIPID DROPLETS; GLUT4; TRANSLOCATION; 3T3-L1; ADIPOCYTES; SYNTAXIN-4; GLYCOGEN; FUSION;
D O I
10.2337/db09-1503
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE-Our previous studies suggest that the SNARE protein synaptosomal-associated protein of 23 kDa (SNAP23) is involved in the link between increased lipid levels and insulin resistance in cardiomyocytes. The objective was to determine whether SNAP23 may also be involved in the known association between lipid accumulation in skeletal muscle and insulin resistance/type 2 diabetes in humans, as well as to identify a potential regulator of SNAP23. RESEARCH DESIGN AND METHODS-We analyzed skeletal muscle biopsies from patients with type 2 diabetes and healthy, insulin-sensitive control subjects for expression (mRNA and protein) and intracellular localization (subcellular fractionation and immunohistochemistry) of SNAP23, and for expression of proteins known to interact with SNARE proteins. Insulin resistance was determined by a euglycemic hyperinsulinemic clamp Potential mechanisms for regulation of SNAP23 were also investigated in the skeletal muscle cell line L6. RESULTS-We showed increased SNAP23 levels in skeletal muscle from patients with type 2 diabetes compared with that from lean control subjects Moreover, SNAP23 was redistributed from the plasma membrane to the microsomal/cytosolic compartment in the patients with the type 2 diabetes Expression of the SNARE-interacting protein Munc18c was higher in skeletal muscle from patients with type 2 diabetes Studies in L6 cells showed that Munc18c promoted the expression of SNAP23. CONCLUSIONS-We have translated our previous in vitro results into humans by showing that there is a change in the distribution of SNAP23 to the interior of the cell in skeletal muscle from patients with type 2 diabetes. We also showed that Munc18c is a potential regulator of SNAP23. Diabetes 59: 1870-1878, 2010
引用
收藏
页码:1870 / 1878
页数:9
相关论文
共 31 条
[1]   PLD1 and ERK2 regulate cytosolic lipid droplet formation [J].
Andersson, Linda ;
Bostrom, Pontus ;
Ericson, Johanna ;
Rutberg, Mikael ;
Magnusson, Bjorn ;
Marchesan, Denis ;
Ruiz, Michel ;
Asp, Lennart ;
Huang, Ping ;
Frohman, Michael A. ;
Boren, Jan ;
Olofsson, Sven-Olof .
JOURNAL OF CELL SCIENCE, 2006, 119 (11) :2246-2257
[2]   Characterization of two distinct binding modes between syntaxin 4 and Munc18c [J].
Aran, Veronica ;
Brandie, Fiona M. ;
Boyd, Alasdair R. ;
Kantidakis, Theodoros ;
Rideout, Elizabeth J. ;
Kelly, Sharon M. ;
Gould, Gwyn W. ;
Bryant, Nia J. .
BIOCHEMICAL JOURNAL, 2009, 419 :655-660
[3]   Skeletal muscle munc18c and syntaxin 4 in human obesity [J].
Bergman, Bryan C. ;
Cornier, Marc-Andre ;
Horton, Tracy J. ;
Bessesen, Daniel H. ;
Eckel, Robert H. .
NUTRITION & METABOLISM, 2008, 5 (1)
[4]   SNARE proteins mediate fusion between cytosolic lipid droplets and are implicated in insulin sensitivity [J].
Bostrom, Pontus ;
Andersson, Linda ;
Rutberg, Mikael ;
Perman, Jeanna ;
Lidberg, Ulf ;
Johansson, Bengt R. ;
Fernandez-Rodriguez, Julia ;
Ericson, Johanna ;
Nilsson, Tommy ;
Boren, Jan ;
Olofsson, Sven-Olof .
NATURE CELL BIOLOGY, 2007, 9 (11) :1286-U139
[5]   Negative Regulation of Syntaxin4/SNAP-23/VAMP2-Mediated Membrane Fusion by Munc18c In Vitro [J].
Brandie, Fiona M. ;
Aran, Veronica ;
Verma, Avani ;
McNew, James A. ;
Bryant, Nia J. ;
Gould, Gwyn W. .
PLOS ONE, 2008, 3 (12)
[6]   The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis [J].
Brasaemle, Dawn L. .
JOURNAL OF LIPID RESEARCH, 2007, 48 (12) :2547-2559
[7]   Proteomic analysis of proteins associated with lipid droplets of basal and lipolytically stimulated 3T3-L1 adipocytes [J].
Brasaemle, DL ;
Dolios, G ;
Shapiro, L ;
Wang, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (45) :46835-46842
[8]   Identification and characterization of Snapin as a ubiquitously expressed SNARE-binding protein that interacts with SNAP23 in non-neuronal cells [J].
Buxton, P ;
Zhang, XM ;
Walsh, B ;
Sriratana, A ;
Schenberg, I ;
Manickam, E ;
Rowe, T .
BIOCHEMICAL JOURNAL, 2003, 375 :433-440
[9]   Insulin Resistance Is Associated With Higher Intramyocellular Triglycerides in Type I but Not Type II Myocytes Concomitant With Higher Ceramide Content [J].
Coen, Paul M. ;
Dube, John J. ;
Amati, Francesca ;
Stefanovic-Racic, Maja ;
Ferrell, Robert E. ;
Toledo, Frederico G. S. ;
Goodpaster, Bret H. .
DIABETES, 2010, 59 (01) :80-88
[10]   Munc18c interaction with syntaxin 4 monomers and SNARE complex intermediates in GLUT4 vesicle trafficking [J].
D'Andrea-Merrins, Matthew ;
Chang, Louise ;
Lam, Alice D. ;
Ernst, Stephen A. ;
Stuenkel, Edward L. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (22) :16553-16566