title: The SNARE protein SNAP23 and the SNARE-interacting protein Munc18c in human skeletal muscle are implicated in insulin resistance/type 2 diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Pontus
authors.initials: P
authors.lastname: Boström
authors.forename: Linda
authors.initials: L
authors.lastname: Andersson
authors.forename: Birgitte
authors.initials: B
authors.lastname: Vind
authors.forename: Liliana
authors.initials: L
authors.lastname: Håversen
authors.forename: Mikael
authors.initials: M
authors.lastname: Rutberg
authors.forename: Ylva
authors.initials: Y
authors.lastname: Wickström
authors.forename: Erik
authors.initials: E
authors.lastname: Larsson
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Jansson
authors.forename: Maria K
authors.initials: MK
authors.lastname: Svensson
authors.forename: Richard
authors.initials: R
authors.lastname: Brånemark
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
authors.forename: Jan
authors.initials: J
authors.lastname: Borén
authors.forename: Kurt
authors.initials: K
authors.lastname: Højlund
authors.forename: Sven-Olof
authors.initials: SO
authors.lastname: Olofsson
mesh_terms: D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D004777:Environment; D005786:Gene Expression Regulation; D015309:Glucose Clamp Technique; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008862:Microsomes, Liver / Q000378:metabolism; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D014430:Twins, Monozygotic
chemical_list: D001786:Blood Glucose; D051938:Munc18 Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C100493:SNAP23 protein, human; D051057:Proto-Oncogene Proteins c-akt
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