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To study the effect of sulfatide on gene expression and proliferation of human primary fibroblasts induced by insulin, insulin-like growth factor-1 and human growth hormone. Human primary fibroblasts were exposed to 1, 3 and 30 μM of sulfatide or its precursor galactosylceramide (GalCer). Proliferation was determined by 3 H-thymidine incorporation and gene expression via microarray analysis. Sulfatide and GalCer reduced the growth rate of fibroblasts by 32%-82% when exposed to 0.5 nM insulin. After challenge with 120 μM of H2 O2 , sulfatide reduced membrane leakage. Fibroblast gene expression was altered by sulfatide in gene pathways associated with cell cycle/growth, transforming growth factor-β function, and encoding of proteins involved in intracellular signalling. NFKBIA, a key control element in NF-кB regulation, was decreased 2-fold by sulfatide. Sulfatide strongly inhibits fibroblast growth. We therefore suggest the addition of sulfatide to injectable commercial insulin formulations, which would reduce adverse fibroblast growth and improve well-being in patients with diabetes. © 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Citation

Allan Roeske-Nielsen, Jan-Eric Månsson, Hasim Tekin, Klaus Rieneck, Klaus Bendtzen, Karsten Buschard. Sulfatide inhibits fibroblast growth, activation and oxidative stress induced by ectopic insulin. Diabetes, obesity & metabolism. 2023 Sep;25(9):2514-2525

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PMID: 37246802

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