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A Peri, Clinical Physiopathology, University of Florence, Florence, 50139, Italy
S Giannini, Diabetes and Metabolic Disease Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy
C Manuelli, Institute of Dermatology and Venereology, University of Florence, Florence, Italy
P Luciani, Clinical Physiopathology, University of Florence, Florence, Italy
A Pezzatini, Diabetes and Metabolic Diseases Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy
S Benvenuti, Florence, Italy
I Cellai, Florence, Italy
C Deledda, Florence, Italy
G Vannelli, Department of Anatomy, Histology and Forensic Medicine, University of Florence, Florence, Italy
M Serio, Florence, Italy
C Rotella, Diabetes and Metabolic Diseases Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy
E Maneschi, Clinical Physiopathology, Endocrine Unit, Univ. of Florence, Florence, Italy

Correspondence: Alessandro Peri, Email: a.peri{at}dfc.unifi.it

Abstract

The exposure of neurons to high glucose concentrations is considered a determinant of diabetic neuropathy, whereas members of the Insulin-like Growth Factor (IGF) system are 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). These cells express the IGF-I receptor, and express and release in the culture medium IGFBP2, IGFBP4 and IGF-I. The release of IGF-I was significantly increased by 17β-estradiol (10 nM). IGF-I (100 nM) treatment determined a significant increase of IGFBP-2 and a decrease of IGFBP-4 release. In addition, IGF-I (1-100 nM) stimulated FNC cell proliferation in a dose-dependent manner. We hypothesized that this effect may be, at least partially, due to IGF-I-induced up-regulation of the expression of the Alzheimer’s disease related gene seladin-1, 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 IGF-I and IGFBP-2 in the culture medium and inhibited FNC growth by inducing apoptosis. The latter was prevented by the addition of IGF-I to the culture medium. Furthermore, high glucose concentrations reduced the expression of seladin-1. 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 trophic effects exerted by the IGF system, and suggest the involvement of the neuroprotective factor seladin-1.

This article has been cited by other articles:

				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]