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¹ Diabetes and Metabolic Diseases Unit² Endocrine Unit, Department of Clinical Physiopathology, Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies (DENOThe)³ Institute of Dermatology and Venereology⁴ Department of Anatomy, Histology and Forensic Medicine, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy

(Correspondence should be addressed to A Peri; Email: a.peri{at}dfc.unifi.it)

The exposure of neurons to high glucose concentrations is considered a determinant of diabetic neuropathy, whereas members of the IGF system are neurotropic factors. Here, we investigated the effects of constant and intermittent high glucose concentrations on IGF1 and IGF-binding proteins (IGFBPs) in human neuroblast long-term cell cultures fetal neuroepithelial cells (FNC). These cells express the IGF1 receptor, and express and release in the culture medium IGFBP2, IGFBP4, and IGF1. The release of IGF1 was significantly increased by 17β-estradiol (10 nM). IGF1 (100 nM) treatment determined a significant increase of IGFBP2 and a decrease of IGFBP4 release. In addition, IGF1 (1–100 nM) stimulated FNC cell proliferation in a dose-dependent manner. We hypothesized that this effect may be, at least partially, due to IGF1-induced up-regulation of the expression of the Alzheimer's disease related gene SELADIN-1 (now known as DHCR24 ), which acts as a pro-survival factor for neuronal cells. Conversely, the exposure to intermittent (20/10 mM), but not stable (20 mM), high glucose concentrations decreased the release of IGF1 and IGFBP2 in the culture medium and inhibited FNC growth by inducing apoptosis. The latter was prevented by the addition of IGF1 to the culture medium. Furthermore, high glucose concentrations reduced the expression of DHCR24. In conclusion, our results indicate 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 tropic effects exerted by the IGF system, and suggest the involvement of the neuroprotective factor DHCR24.

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				A. Peri and M. Serio Neuroprotective effects of the Alzheimer's disease-related gene seladin-1 J. Mol. Endocrinol., November 1, 2008; 41(5): 251 - 261. [Abstract] [Full Text] [PDF]