The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes
(2010) In Diabetes 59(8). p.1870-1878- Abstract
- 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... (More)
- 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 (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1676798
- author
- Bostrom, Pontus
; Andersson, Linda
; Vind, Birgitte
; Haversen, Liliana
; Rutberg, Mikael
; Wickstrom, Ylva
; Larsson, Erik
; Jansson, Per-Anders
; Svensson, Maria K.
; Branemark, Richard
; Ling, Charlotte
LU
; Beck-Nielsen, Henning
; Boren, Jan
; Hojlund, Kurt
and Olofsson, Sven-Olof
(Less) - organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Diabetes
- volume
- 59
- issue
- 8
- pages
- 1870 - 1878
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- wos:000280749100005
- scopus:77955400118
- pmid:20460426
- ISSN
- 1939-327X
- DOI
- 10.2337/db09-1503
- language
- English
- LU publication?
- yes
- id
- 45f36f9c-c6ca-467f-9cb7-158ac2d67cda (old id 1676798)
- date added to LUP
- 2016-04-01 15:05:22
- date last changed
- 2024-05-10 06:31:16
@article{45f36f9c-c6ca-467f-9cb7-158ac2d67cda,
abstract = {{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}},
author = {{Bostrom, Pontus and Andersson, Linda and Vind, Birgitte and Haversen, Liliana and Rutberg, Mikael and Wickstrom, Ylva and Larsson, Erik and Jansson, Per-Anders and Svensson, Maria K. and Branemark, Richard and Ling, Charlotte and Beck-Nielsen, Henning and Boren, Jan and Hojlund, Kurt and Olofsson, Sven-Olof}},
issn = {{1939-327X}},
language = {{eng}},
number = {{8}},
pages = {{1870--1878}},
publisher = {{American Diabetes Association Inc.}},
series = {{Diabetes}},
title = {{The SNARE Protein SNAP23 and the SNARE-Interacting Protein Munc18c in Human Skeletal Muscle Are Implicated in Insulin Resistance/Type 2 Diabetes}},
url = {{http://dx.doi.org/10.2337/db09-1503}},
doi = {{10.2337/db09-1503}},
volume = {{59}},
year = {{2010}},
}