Characterization of diabetic neuropathy in the Zucker diabetic Sprague-Dawley rat: a new animal model for type 2 diabetes

Eric P Davidson; Lawrence J Coppey; Amey Holmes; Sergey Lupachyk; Brian L Dake; Christine L Oltman; Richard G Peterson; Mark A Yorek

doi:10.1155/2014/714273

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Characterization of diabetic neuropathy in the Zucker diabetic Sprague-Dawley rat: a new animal model for type 2 diabetes

Journal article

Open access

Peer reviewed

Characterization of diabetic neuropathy in the Zucker diabetic Sprague-Dawley rat: a new animal model for type 2 diabetes

Eric P Davidson, Lawrence J Coppey, Amey Holmes, Sergey Lupachyk, Brian L Dake, Christine L Oltman, Richard G Peterson and Mark A Yorek

Journal of diabetes research, Vol.2014, 714273

2014

DOI: 10.1155/2014/714273

PMCID: PMC4211210

PMID: 25371906

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https://doi.org/10.1155/2014/714273View

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Abstract

Recently a new rat model for type 2 diabetes the Zucker diabetic Sprague-Dawley (ZDSD/Pco) was created. In this study we sought to characterize the development of diabetic neuropathy in ZDSD rats using age-matched Sprague-Dawley rats as a control. Rats were examined at 34 weeks of age 12 weeks after the onset of hyperglycemia in ZDSD rats. At this time ZDSD rats were severely insulin resistant with slowing of both motor and sensory nerve conduction velocities. ZDSD rats also had fatty livers, elevated serum free fatty acids, triglycerides, and cholesterol, and elevated sciatic nerve nitrotyrosine levels. The corneas of ZDSD rats exhibited a decrease in subbasal epithelial corneal nerves and sensitivity. ZDSD rats were hypoalgesic but intraepidermal nerve fibers in the skin of the hindpaw were normal compared to Sprague-Dawley rats. However, the number of Langerhans cells was decreased. Vascular reactivity of epineurial arterioles, blood vessels that provide circulation to the sciatic nerve, to acetylcholine and calcitonin gene-related peptide was impaired in ZDSD rats. These data indicate that ZDSD rats develop many of the neural complications associated with type 2 diabetes and are a good animal model for preclinical investigations of drug development for diabetic neuropathy.

Age Factors

Animals

Arterioles - physiopathology

Blood Glucose - metabolism

Cholesterol - blood

Diabetes Mellitus, Type 2 - blood

Diabetes Mellitus, Type 2 - complications

Diabetes Mellitus, Type 2 - physiopathology

Diabetic Angiopathies - etiology

Diabetic Angiopathies - physiopathology

Diabetic Neuropathies - blood

Diabetic Neuropathies - etiology

Diabetic Neuropathies - pathology

Diabetic Neuropathies - physiopathology

Disease Models, Animal

Fatty Acids, Nonesterified - blood

Fatty Liver - blood

Fatty Liver - etiology

Langerhans Cells - pathology

Male

Neural Conduction

Nociception

Rats, Sprague-Dawley

Rats, Zucker

Sciatic Nerve - metabolism

Sciatic Nerve - physiopathology

Time Factors

Triglycerides - blood

Tyrosine - analogs & derivatives

Tyrosine - metabolism

Vasodilation

Details

Title: Subtitle: Characterization of diabetic neuropathy in the Zucker diabetic Sprague-Dawley rat: a new animal model for type 2 diabetes
Creators: Eric P Davidson - University of Iowa
Lawrence J Coppey - University of Iowa
Amey Holmes - Iowa City VA Health Care System
Sergey Lupachyk - University of Iowa
Brian L Dake - University of Iowa
Christine L Oltman - Iowa City VA Health Care System
Richard G Peterson - PreClinOmics (United States)
Mark A Yorek - United States Department of Veterans Affairs
Resource Type: Journal article
Publication Details: Journal of diabetes research, Vol.2014, 714273
DOI: 10.1155/2014/714273
PMID: 25371906
PMCID: PMC4211210
NLM abbreviation: J Diabetes Res
ISSN: 2314-6745
eISSN: 2314-6753
Grant note: I01 BX001680 / BLRD VA I01 RX000889 / RRD VA
Language: English
Date published: 2014
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984360060102771

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