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

Eric Davidson; Lawrence Coppey; Bao Lu; Victor Arballo; Nigel A Calcutt; Craig Gerard; Mark Yorek

doi:10.1155/2009/431980

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

Journal article

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

Eric Davidson, Lawrence Coppey, Bao Lu, Victor Arballo, Nigel A Calcutt, Craig Gerard and Mark Yorek

Experimental diabetes research, Vol.2009, 431980

2009

DOI: 10.1155/2009/431980

PMCID: PMC2817866

PMID: 20148083

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Abstract

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.

Details

Title: Subtitle: The Roles of Streptozotocin Neurotoxicity and Neutral Endopeptidase in Murine Experimental Diabetic Neuropathy
Creators: Eric Davidson - Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA, Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
Lawrence Coppey - Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA, Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
Bao Lu - Ina Sue Perlmutter Laboratory, Department of Pediatrics and Medicine, Harvard Medical School, Children's Hospital, Boston, MA 02115, USA
Victor Arballo - Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA
Nigel A Calcutt - Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA
Craig Gerard - Ina Sue Perlmutter Laboratory, Department of Pediatrics and Medicine, Harvard Medical School, Children's Hospital, Boston, MA 02115, USA
Mark Yorek - Department of Veterans Affairs Iowa City Health Care System, University of Iowa, Iowa City, IA 52246, USA, Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA
Resource Type: Journal article
Publication Details: Experimental diabetes research, Vol.2009, 431980
DOI: 10.1155/2009/431980
PMID: 20148083
PMCID: PMC2817866
NLM abbreviation: Exp Diabetes Res
ISSN: 1687-5214
eISSN: 1687-5303
Grant note: DOI: 10.13039/100000901, name: Juvenile Diabetes Research Foundation International, award: DK073990, DK92889, DK057629
Language: English
Date published: 2009
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094652402771

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