ArticleNutrition & metabolism2008
Skeletal muscle munc18c and syntaxin 4 in human obesity.
Article in Nutrition & metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Bioinformatics-led identification of pathophysiological hallmark genes in diabesotension via graph clustering method.Journal of diabetes and metabolic disorders · 2025Article
- Targeted stabilization of Munc18-1 function via pharmacological chaperones.EMBO molecular medicine · 2021Article
- Exocytosis proteins as novel targets for diabetes prevention and/or remediation?American journal of physiology. Regulatory, integrative and comparative physiology · 2017Review
- Munc18c mediates exocytosis of pre-docked and newcomer insulin granules underlying biphasic glucose stimulated insulin secretion in human pancreatic beta-cells.Molecular metabolism · 2015Article
- Doc2b serves as a scaffolding platform for concurrent binding of multiple Munc18 isoforms in pancreatic islet β-cells.The Biochemical journal · 2014Article
- Regulation of the SNARE-interacting protein Munc18c tyrosine phosphorylation in adipocytes by protein-tyrosine phosphatase 1B.Cell communication and signaling : CCS · 2013Article
- Munc18c in adipose tissue is downregulated in obesity and is associated with insulin.PloS one · 2013Article
- Doc2b is a key effector of insulin secretion and skeletal muscle insulin sensitivity.Diabetes · 2012Article
- Munc18c phosphorylation by the insulin receptor links cell signaling directly to SNARE exocytosis.The Journal of cell biology · 2011Article
- Article
- Exocytosis mechanisms underlying insulin release and glucose uptake: conserved roles for Munc18c and syntaxin 4.American journal of physiology. Regulatory, integrative and comparative physiology · 2010Review
- Article
- Involvement of TNF-alpha in abnormal adipocyte and muscle sortilin expression in obese mice and humans.Diabetologia · 2009Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAnimal and cell culture data suggest a critical role for Munc18c and Syntaxin 4 proteins in insulin mediated glucose transport in skeletal muscle, but no studies have been published in humans.
methodsWe investigated the effect of a 12 vs. 48 hr fast on insulin action and skeletal muscle Munc18c and Syntaxin 4 protein in lean and obese subjects. Healthy lean (n = 14; age = 28.0 +/- 1.4 yr; BMI = 22.8 +/- 0.42 kg/m2) and obese subjects (n = 11; age = 34.6 +/- 2.3 yr; BMI = 36.1 +/- 1.5 kg/m2) were studied twice following a 12 and 48 hr fast. Skeletal muscle biopsies were obtained before a 3 hr 40 mU/m2/min hyperinsulinemic-euglycemic clamp with [6,6-2H2]glucose infusion.
resultsGlucose rate of disappearance (Rd) during the clamp was lower in obese vs. lean subjects after the 12 hr fast (obese: 6.25 +/- 0.67 vs. lean: 9.42 +/- 1.1 mg/kgFFM/min, p = 0.007), and decreased significantly in both groups after the 48 hr fast (obese 3.49 +/- 0.31 vs. lean: 3.91 +/- 0.42 mg/kgFFM/min, p = 0.002). Munc18c content was not significantly different between lean and obese subjects after the 12 hour fast, and decreased after the 48 hr fast in both groups (p = 0.013). Syntaxin 4 content was not altered by obesity or fasting duration. There was a strong positive relationship between plasma glucose concentration and Munc18c content in lean and obese subjects during both 12 and 48 hr fasts (R2 = 0.447, p = 0.0015). Significant negative relationships were also found between Munc18c and FFA (p = 0.041), beta-hydroxybutyrate (p = 0.039), and skeletal muscle AKT content (p = 0.035) in lean and obese subjects.
conclusionThese data indicate Munc18c and Syntaxin 4 are present in human skeletal muscle. Munc18c content was not significantly different between lean and obese subjects, and is therefore unlikely to explain obesity-induced insulin resistance. Munc18c content decreased after prolonged fasting in lean and obese subjects concurrently with reduced insulin action. These data suggest changes in Munc18c content in skeletal muscle are associated with short-term changes in insulin action in humans.
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Registered trials
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