Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals

Xi Wang,1 Debra C DuBois,1,2 Siddharth Sukumaran,2 Vivaswath Ayyar,1 William J Jusko,2,3 Richard R Almon1–3 1Department of Biological Sciences, 2Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA; 3New York State Center of Excellence in Bioinf...

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Autores principales:	Wang X, DuBois DC, Sukumaran S, Ayyar V, Jusko WJ, Almon RR
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/c265bdac26de4e8cb4afed86dbcdb36e
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spelling	oai:doaj.org-article:c265bdac26de4e8cb4afed86dbcdb36e2021-12-02T07:44:56ZVariability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals1178-7007https://doaj.org/article/c265bdac26de4e8cb4afed86dbcdb36e2014-11-01T00:00:00Zhttp://www.dovepress.com/variability-in-zucker-diabetic-fatty-rats-differences-in-disease-progr-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007 Xi Wang,1 Debra C DuBois,1,2 Siddharth Sukumaran,2 Vivaswath Ayyar,1 William J Jusko,2,3 Richard R Almon1–3 1Department of Biological Sciences, 2Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA; 3New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA Abstract: Both obesity and chronic inflammation are often associated with insulin resistance and type 2 diabetes. The Zucker diabetic fatty (ZDF) rat (fa/fa) is an obese animal model frequently used in type 2 diabetes research. The current study determines whether chronic administration (from 5 weeks of age through 24 weeks of age) of salsalate, a salicylate with anti-inflammatory properties, would be effective in mitigating diabetes disease progression in ZDF rats. Although a trend existed for lower blood glucose in the salsalate-treated group, significant differences were obscured by high animal-level variability. However, even in the non-drug-treated group, not all ZDF rats became diabetic as expected. Therefore, animals were parsed into two groups, regardless of drug treatment: normoglycemic ZDF rats, which maintained blood glucose profiles identical to nondiabetic Zucker lean rats (ZLRs), and hyperglycemic ZDF rats, which exhibited progressive elevation in blood glucose. To ascertain the differences between ZDF rats that became hyperglycemic and those that did not, relevant physiological indices and expression levels of adiponectin, tumor necrosis factor-α, interleukin-6, and glucocorticoid-induced leucine zipper messenger RNAs in adipose tissue were measured at sacrifice. Plasma C-reactive protein concentrations and expression levels of cytokine and glucocorticoid-induced leucine zipper messenger RNAs suggested more prevalent chronic inflammation in hyperglycemic animals. Early elevation of the insulin-sensitizing adipokine, adiponectin, was present in both ZDF groups, with the rate of its age-related decline faster in hyperglycemic animals. The most marked difference between the two groups of ZDF animals was in insulin output. Although the two ZDF populations had very similar elevated plasma insulin concentrations for the first 10 weeks, after that time, plasma insulin decreased markedly in the animals that became hyperglycemic, whereas it remained high in the normoglycemic ZDF rats. Thus, hyperglycemic ZDF animals exhibit both insulin resistance and progressive beta cell failure, whereas normoglycemic ZDF rats exhibit a lesser degree of insulin resistance that does not progress to beta cell failure. In these respects, the normoglycemic ZDF rats appear to revert back to a phenotype that strongly resembles that of nondiabetic Zucker fatty rats from which they were derived. Keywords: type 2 diabetes, ZDF rats, animal modelsWang XDuBois DCSukumaran SAyyar VJusko WJAlmon RRDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2014, Iss default, Pp 531-541 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Wang X DuBois DC Sukumaran S Ayyar V Jusko WJ Almon RR Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals
description	Xi Wang,1 Debra C DuBois,1,2 Siddharth Sukumaran,2 Vivaswath Ayyar,1 William J Jusko,2,3 Richard R Almon1–3 1Department of Biological Sciences, 2Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA; 3New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA Abstract: Both obesity and chronic inflammation are often associated with insulin resistance and type 2 diabetes. The Zucker diabetic fatty (ZDF) rat (fa/fa) is an obese animal model frequently used in type 2 diabetes research. The current study determines whether chronic administration (from 5 weeks of age through 24 weeks of age) of salsalate, a salicylate with anti-inflammatory properties, would be effective in mitigating diabetes disease progression in ZDF rats. Although a trend existed for lower blood glucose in the salsalate-treated group, significant differences were obscured by high animal-level variability. However, even in the non-drug-treated group, not all ZDF rats became diabetic as expected. Therefore, animals were parsed into two groups, regardless of drug treatment: normoglycemic ZDF rats, which maintained blood glucose profiles identical to nondiabetic Zucker lean rats (ZLRs), and hyperglycemic ZDF rats, which exhibited progressive elevation in blood glucose. To ascertain the differences between ZDF rats that became hyperglycemic and those that did not, relevant physiological indices and expression levels of adiponectin, tumor necrosis factor-α, interleukin-6, and glucocorticoid-induced leucine zipper messenger RNAs in adipose tissue were measured at sacrifice. Plasma C-reactive protein concentrations and expression levels of cytokine and glucocorticoid-induced leucine zipper messenger RNAs suggested more prevalent chronic inflammation in hyperglycemic animals. Early elevation of the insulin-sensitizing adipokine, adiponectin, was present in both ZDF groups, with the rate of its age-related decline faster in hyperglycemic animals. The most marked difference between the two groups of ZDF animals was in insulin output. Although the two ZDF populations had very similar elevated plasma insulin concentrations for the first 10 weeks, after that time, plasma insulin decreased markedly in the animals that became hyperglycemic, whereas it remained high in the normoglycemic ZDF rats. Thus, hyperglycemic ZDF animals exhibit both insulin resistance and progressive beta cell failure, whereas normoglycemic ZDF rats exhibit a lesser degree of insulin resistance that does not progress to beta cell failure. In these respects, the normoglycemic ZDF rats appear to revert back to a phenotype that strongly resembles that of nondiabetic Zucker fatty rats from which they were derived. Keywords: type 2 diabetes, ZDF rats, animal models
format	article
author	Wang X DuBois DC Sukumaran S Ayyar V Jusko WJ Almon RR
author_facet	Wang X DuBois DC Sukumaran S Ayyar V Jusko WJ Almon RR
author_sort	Wang X
title	Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals
title_short	Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals
title_full	Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals
title_fullStr	Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals
title_full_unstemmed	Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals
title_sort	variability in zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/c265bdac26de4e8cb4afed86dbcdb36e
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Variability in Zucker diabetic fatty rats: differences in disease progression in hyperglycemic and normoglycemic animals

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