Journal article
Vascular and Neural Complications in Type 2 Diabetic Rats: Improvement by Sacubitril/Valsartan Greater Than Valsartan Alone
Diabetes (New York, N.Y.), Vol.67(8), pp.1616-1626
08/01/2018
DOI: 10.2337/db18-0062
PMID: 29941448
Abstract
Previously, we had shown that a vasopeptidase inhibitor drug containing ACE and neprilysin inhibitors was an effective treatment for diabetic vascular and neural complications. However, side effects prevented further development. This led to the development of sacubitril/valsartan, a drug containing angiotensin II receptor blocker and neprilysin inhibitor that we hypothesized would be an effective treatment for diabetic peripheral neuropathy. Using early and late intervention protocols (4 and 12 weeks posthyperglycemia, respectively), type 2 diabetic rats were treated with valsartan or sacubitril/valsartan for 12 weeks followed by an extensive evaluation of vascular and neural end points. The results demonstrated efficacy of sacubitril/valsartan in improving vascular and neural function was superior to valsartan alone. In the early intervention protocol, sacubitril/valsartan treatmentwas found to slow progression of these deficits and, with late intervention treatment, was found to stimulate restoration of vascular reactivity, motor and sensory nerve conduction velocities, and sensitivity/regeneration of sensory nerves of the skin and cornea in a rat model of type 2 diabetes. These preclinical studies suggest that sacubitril/valsartanmay be an effective treatment for diabetic peripheral neuropathy, but additional studies will be needed to investigate these effects further.
Details
- Title: Subtitle
- Vascular and Neural Complications in Type 2 Diabetic Rats: Improvement by Sacubitril/Valsartan Greater Than Valsartan Alone
- Creators
- Eric P. Davidson - University of IowaLawrence J. Coppey - University of IowaHanna Shevalye - University of IowaAlexander Obrosov - University of IowaMark A. Yorek - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Diabetes (New York, N.Y.), Vol.67(8), pp.1616-1626
- Publisher
- Amer Diabetes Assoc
- DOI
- 10.2337/db18-0062
- PMID
- 29941448
- ISSN
- 0012-1797
- eISSN
- 1939-327X
- Number of pages
- 11
- Grant note
- LCZ696BUS10T / Novartis
- Language
- English
- Date published
- 08/01/2018
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984359664102771
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