C-Peptide Prevents Hippocampal Apoptosis in Type 1 Diabetes英文文献资料.docVIP

Int. Jnl. Experimental Diab. Res., 3:241–245, 2002 Copyrightc 2002 Taylor Francis 1560–4284/02 $12.00 + .00 DOI: 10.1080/15604280290013991 C-peptidePreventsHippocampalApoptosis inType1Diabetes Zhen-guo Li,1,3 Weixian Zhang,1,3 and Anders A. F. Sima1,2,3 Departments of 1Pathology, 2Neurology, and 3Morris J. Hood Jr. Comprehensive Diabetes Center, Wayne State University School of Medicine, Detroit, Michigan, USA dren with type 1 diabetes [2]. Experimentally, spatial learning To explore mechanisms underlying central nervous system de?cits in streptozotocin (STZ)-diabetic rats have been asso- (CNS) complications in diabetes, we examined hippocampal neu- ronal 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 demonstrated a duration-related asynchronous apoptosis of hip- ciated with altered synaptic integrity of hippocampus, ?ndings which were modi?ed by low doses of insulin [3]. We recently apoptotic cells, and an elevated ratio of Bax/Bcl-x L, accompanied by reduced neuronal density in the hippocampus. No apoptotic ac- tivitywasdetectedandneuronaldensitywasunchangedin2-month diabetichippocampus,whereasinsulin-likegrowthfactor(IGF)ac- pocampalneuronsinthespontaneouslytype1diabeticBB/Wrat [4], which resulted in a 34% loss of CA1 neurons after 8 months of diabetes. These changes were preceded and accompanied by tivities were impaired. In type 1 diabetic BB/W rats replaced with a signi?cant down-regulation of the hippocampal insulin-like C-peptide, no TdT-mediated dUTP nick-end labeling (TUNEL)- growth factor (IGF) system consisting of IGF-1, IGF-2, IGF-1 positive cells were shown and DNA laddering was not evident in receptor (IGF-IR), and insulin receptor (IR) [4, 5]. Because both hippocampusateither2or8months.C-peptideadministrationpre- vented the preceding perturbation of IGF expression and reduced IGF-1andin