The Roles of Streptozotocin Neurotoxicity and Neutral Endopeptidase in Murine Experimental Diabetic Neuropathy

被引:57
作者
Davidson, Eric [1 ,2 ]
Coppey, Lawrence [1 ,2 ]
Lu, Bao [3 ]
Arballo, Victor [4 ]
Calcutt, Nigel A. [4 ]
Gerard, Craig [3 ]
Yorek, Mark [1 ,2 ]
机构
[1] Univ Iowa, Dept Vet Affairs Iowa City Hlth Care Syst, Iowa City, IA 52246 USA
[2] Univ Iowa, Dept Internal Med, Iowa City, IA 52246 USA
[3] Harvard Univ, Childrens Hosp, Sch Med, Ina Sue Perlmutter Lab,Dept Pediat & Med, Boston, MA 02115 USA
[4] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA
关键词
IMPAIRED GLUCOSE-TOLERANCE; ANGIOTENSIN-CONVERTING ENZYME; ALDOSE REDUCTASE INHIBITION; PERIPHERAL NERVOUS-SYSTEM; VASOPEPTIDASE INHIBITION; FATTY RATS; NEURAL DYSFUNCTION; NEUROGENIC INFLAMMATION; CHORIOCARCINOMA CELLS; SENSORY NEURONS;
D O I
10.1155/2009/431980
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
We demonstrated that inhibition of neutral endopeptidase (NEP), a protease that degrades vaso- and neuroactive peptides, improves vascular and neural function in diabetic animal models. In this study we explored the role of NEP in neuropathy related to either insulin deficient diabetes or diet-induced obesity using NEP deficient (-/-) mice. Initial studies showed that streptozotocin, in the absence of subsequent hyperglycemia, did not induce nerve conduction slowing or paw thermal hypoalgesia. Glucose disposal was impaired in both C57Bl/6 and NEP -/- mice fed a high fat diet. Thermal hypoalgesia and nerve conduction slowing were present in both streptozotocin-diabetic and high fat fed C57Bl/6 mice but not in NEP -/- mice exposed to either streptozotocin-induced diabetes or a high fat diet. These studies suggest that streptozotocin does not induce neurotoxicity in mice and that NEP plays a role in regulating nerve function in insulin-deficient diabetes and diet-induced obesity. Copyright (C) 2009 Eric Davidson et al.
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页数:9
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