Characterization of diabetic neuropathy in the Zucker diabetic Sprague-Dawley rat: a new animal model for type 2 diabetes.
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.
Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Eric P
EP
Davidson
Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Lawrence J
LJ
Coppey
Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA 52246, USA.
Amey
A
Holmes
Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Sergey
S
Lupachyk
Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA.
Brian L
BL
Dake
Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA 52246, USA.
Christine L
CL
Oltman
PreClinOmics Inc., Indianapolis, IN 46268, USA.
Richard G
RG
Peterson
Department of Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA ; Department of Veterans Affairs Iowa City Health Care System, Iowa City, IA 52246, USA ; Iowa City Veterans Administration Center for the Prevention and Treatment of Visual Loss, Iowa City, IA 52246, USA ; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA.
Mark A
MA
Yorek
D000367:Age Factors; D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000209:etiology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000209:etiology; D007801:Langerhans Cells / Q000473:pathology; D008297:Male; D009431:Neural Conduction; D059225:Nociception; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D012584:Sciatic Nerve / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014664:Vasodilation
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; C002744:3-nitrotyrosine; D014443:Tyrosine; D002784:Cholesterol