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

Wang X, DuBois DC, Sukumaran S, Ayyar V, Jusko WJ, Almon RR - Diabetes Metab Syndr Obes (2014)

Bottom Line: Although a trend existed for lower blood glucose in the salsalate-treated group, significant differences were obscured by high animal-level variability.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, State University of New York at Buffalo, 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.

No MeSH data available.


Related in: MedlinePlus

Body weight and food intake.Notes: (A) Body weights, (B) food intake, and (C) food intake normalized to body weight as a function of age in hypoglycemic ZDF rats, normoglycemic ZDF rats, and ZLR. Profiles depict means and one standard deviation.Abbreviations: ZDF, Zucker diabetic fatty; ZLR, Zucker lean rats.
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f4-dmso-7-531: Body weight and food intake.Notes: (A) Body weights, (B) food intake, and (C) food intake normalized to body weight as a function of age in hypoglycemic ZDF rats, normoglycemic ZDF rats, and ZLR. Profiles depict means and one standard deviation.Abbreviations: ZDF, Zucker diabetic fatty; ZLR, Zucker lean rats.

Mentions: Figure 4A shows that both ZDF rats that developed hyperglycemia and those that did not increased body weights at the same rate up to 80 days, but after that time, the weights of those animals that developed hyperglycemia plateaued, whereas those that did not continued to increase. Both groups of ZDF animals consumed more food than ZLR controls (Figure 4B), with hyperglycemic animals consuming more food than normoglycemic ZDF rats at later ages. When food intake was normalized to body weight (Figure 4C), hyperglycemic animals consumed proportionately more food throughout the study. Therefore, the lower body weights in hyperglycemic ZDF animals were not due to decreased appetite/food consumption. Salsalate had no significant effects on body weights or food consumption in either ZDF rats or ZLRs (data not shown).


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

Wang X, DuBois DC, Sukumaran S, Ayyar V, Jusko WJ, Almon RR - Diabetes Metab Syndr Obes (2014)

Body weight and food intake.Notes: (A) Body weights, (B) food intake, and (C) food intake normalized to body weight as a function of age in hypoglycemic ZDF rats, normoglycemic ZDF rats, and ZLR. Profiles depict means and one standard deviation.Abbreviations: ZDF, Zucker diabetic fatty; ZLR, Zucker lean rats.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4234283&req=5

f4-dmso-7-531: Body weight and food intake.Notes: (A) Body weights, (B) food intake, and (C) food intake normalized to body weight as a function of age in hypoglycemic ZDF rats, normoglycemic ZDF rats, and ZLR. Profiles depict means and one standard deviation.Abbreviations: ZDF, Zucker diabetic fatty; ZLR, Zucker lean rats.
Mentions: Figure 4A shows that both ZDF rats that developed hyperglycemia and those that did not increased body weights at the same rate up to 80 days, but after that time, the weights of those animals that developed hyperglycemia plateaued, whereas those that did not continued to increase. Both groups of ZDF animals consumed more food than ZLR controls (Figure 4B), with hyperglycemic animals consuming more food than normoglycemic ZDF rats at later ages. When food intake was normalized to body weight (Figure 4C), hyperglycemic animals consumed proportionately more food throughout the study. Therefore, the lower body weights in hyperglycemic ZDF animals were not due to decreased appetite/food consumption. Salsalate had no significant effects on body weights or food consumption in either ZDF rats or ZLRs (data not shown).

Bottom Line: Although a trend existed for lower blood glucose in the salsalate-treated group, significant differences were obscured by high animal-level variability.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, State University of New York at Buffalo, 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.

No MeSH data available.


Related in: MedlinePlus