Sulfatide inhibits fibroblast growth, activation and oxidative stress induced by ectopic insulin

• Aim: 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. Materials and Methods: Human primary fibroblasts were exposed to 1, 3 and 30 mu M of sulfatide or its precursor galactosylceramide (GalCer). Proliferation was determined by 3H-thymidine incorporation and gene expression via microarray analysis. Results: Sulfatide and GalCer reduced the growth rate of fibroblasts by 32%-82% when exposed to 0.5 nM insulin. After challenge with 120 mu M of H2O2, sulfatide reduced membrane leakage. Fibroblast gene expression was altered by sulfatide in gene pathways associated with cell cycle/growth, transforming growth factor-beta function, and encoding of proteins involved in intracellular signalling. NFKBIA, a key control element in NF-kappa B regulation, was decreased 2-fold by sulfatide. Conclusions: 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

beta cell devices

fibroblasts

sphingolipids

sulfatide

type 1

diabetes

ganglioside-mediated modulation

lindau tumor-suppressor

cell-growth

exogenous glycosphingolipids

tyrosine phosphorylation

hydrogen-peroxide

langerhans

receptor

islets

involvement

Endocrinology & Metabolism

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ref (ämneskategori)

art (ämneskategori)