The exposure of cells to high glucose concentrations is considered a determinant of diabetic neuropathy. Conversely, members of the Insulin-like Growth Factor (IGF) system are well known neurotrophic factors. Here, we investigated the effects of constant and intermittent high glucose concentrations on IGF-I and IGF Binding Proteins (IGFBPs) in human neuroblast long-term cell cultures (FNC). We first demonstrated that FNC express the IGF-I receptor, and express and release in the culture medium IGF-I, IGFBP-2 and IGFBP-4. IGF-I secretion was significantly increased by the exposure to 17β-estradiol (10 nM), in agreement with the reported cross-talk between the IGF system and estrogen in neuronal cells. FNC treatment with IGF-I (100 nM) increased the release of IGFBP-2, that is known to facilitate the binding of IGF-I to its receptor, whereas it reduced the release of IGFBP-4, that is considered an inhibitor of the biological actions of IGF-I. In addition, IGF-I stimulated FNC cell proliferation in a dose-dependent manner (1100 nM). Previous data showed that 17β-estradiol increases the expression of the Alzheimer disease related gene seladin-1, which acts as a pro-survival factor for neuronal cells. Similarly, here we observed that also IGF-I (10 nM) significantly increased the expression of this gene. In contrast with the effects of IGF-I, the exposure to intermittent (20/10 mM), but not stable (20 mM), high glucose concentrations inhibited FNC growth, and determined a decreased release of IGF-I and IGF-BP2. In addition, high glucose decreased the expression of seladin-1. In conclusion, our results suggest for the first time that intermittent high glucose concentrations, similar to those observed in poorly controlled diabetic patients, may contribute to the development of diabetic neuropathy by interfering with the trophic effects exerted by the IGF system, which might be mediated, at least partially, by the pro-survival factor seladin-1.
03 - 07 May 2008
European Society of Endocrinology