C-Peptide Prevents Hippocampal Apoptosis in Type 1 Diabetes |
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| Authors: | Zhen-guo Li Weixian Zhang Anders A F Sima |
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| Institution: | 1. Department of Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA.;2. Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, MI 48201, USA.;3. Morris J. Hood Jr. Comprehensive Diabetes Center, Wayne State University School of Medicine, Detroit, Michigan, USA.;4. Department of Pathology, Wayne State University School of Medicine, Room 9275, H.G. Scott Hall, 540 East Canfield Avenue 48201, Detroit, Michigan, USA, |
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| Abstract: | To explore mechanisms underlying central nervous system
(CNS) complications in diabetes, we examined hippocampal neuronal
apoptosis and loss, and the effect of C-peptide replacement
in type 1 diabetic BB/W rats. Apoptosis was demonstrated after
8 months of diabetes, by DNA fragmentation, increased number of
apoptotic cells, and an elevated ratio of Bax/Bcl-xL, accompanied
by reduced neuronal density in the hippocampus. No apoptotic activity
was detected and neuronal density was unchanged in 2-month
diabetic hippocampus, whereas insulin-like growth factor (IGF) activities
were impaired. In type 1 diabetic BB/W rats replaced with
C-peptide, no TdT-mediated dUTP nick-end labeling (TUNEL)-
positive cells were shown and DNA laddering was not evident in
hippocampus at either 2 or 8 months. C-peptide administration prevented
the preceding perturbation of IGF expression and reduced
the elevated ratio of Bax/Bcl-xL. Our data suggest that type 1 diabetes
causes a duration-dependent programmed cell death of the
hippocampus, which is partially prevented by C-peptide. |
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