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Diabetes disease progression in Goto-Kakizaki rats: effects of salsalate treatment.

Wang X, DuBois DC, Cao Y, Jusko WJ, Almon RR - Diabetes Metab Syndr Obes (2014)

Bottom Line: While this difference in blood glucose between 4 and 21 weeks in GK-S animals was significant, blood glucose at 21 weeks was significantly lower in GK-S compared to GK-C animals.At sacrifice, salsalate decreased plasma insulin (GK-S =1.0±0.3; GK-C =2.0±0.3 ng/mL, P<0.001) and increased plasma adiponectin concentrations (GK-S =15.9±0.7; GK-C =9.7±2.0 μg/mL, P<0.001).These results suggest that salsalate acts to both increase adiponectin and decrease adipose tissue-based inflammation while preventing type 2 diabetes disease progression in GK rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.

ABSTRACT
This study investigates the antidiabetic effects of salsalate on disease progression of diabetes in non-obese diabetic Goto-Kakizaki (GK) rats, an experimental model of type 2 diabetes. Salsalate was formulated in rat chow (1,000 ppm) and used to feed rats from 5 to 21 weeks of age. At 5 weeks of age, GK and Wistar (WIS) control rats were subdivided into four groups, each composed of six rats: GK rats with standard diet (GK-C); GK rats with salsalate-containing diet (GK-S); WIS rats with standard diet (WIS-C); and WIS rats with salsalate-containing diet (WIS-S). The GK-C rats (167.2±11.6 mg/dL) showed higher blood glucose concentrations than WIS-C rats (133.7±4.9 mg/dL, P<0.001) at the beginning of the experiment, and had substantially elevated blood glucose from an age of 15 weeks until sacrifice at 21 weeks (341.0±133.6 mg/dL). The GK-S rats showed an almost flat profile of blood glucose from 4 weeks (165.1±11.0 mg/dL) until sacrifice at 21 weeks of age (203.7±22.2 mg/dL). While this difference in blood glucose between 4 and 21 weeks in GK-S animals was significant, blood glucose at 21 weeks was significantly lower in GK-S compared to GK-C animals. At sacrifice, salsalate decreased plasma insulin (GK-S =1.0±0.3; GK-C =2.0±0.3 ng/mL, P<0.001) and increased plasma adiponectin concentrations (GK-S =15.9±0.7; GK-C =9.7±2.0 μg/mL, P<0.001). Salsalate also lowered total cholesterol in GK-S rats (96.1±8.5 mg/dL) compared with GK-C rats (128.0±11.4 mg/dL, P<0.001). Inflammation-related genes (Ifit1 and Iigp1) exhibited much higher mRNA expression in GK-C rats than WIS-C rats in liver, adipose, and muscle tissues, while salsalate decreased the Ifit1 and Iigp1 mRNA only in adipose tissue. These results suggest that salsalate acts to both increase adiponectin and decrease adipose tissue-based inflammation while preventing type 2 diabetes disease progression in GK rats.

No MeSH data available.


Related in: MedlinePlus

Expression of genes reflecting inflammation in liver tissue with salsalate treatment.Notes: (A) Ifit1 and (B) Iigp1 mRNA measured by qRTPCR in liver tissue samples taken at sacrifice from GK and WIS rats treated with and without salsalate treatment. Histograms represent means and error bars one standard deviation of the mean. **P<0.01.Abbreviations: GK, Goto-Kakizaki; GK-C, GK rats with standard diet; GK-S, GK rats with salsalate-containing diet; qRTPCR, quantitative reverse transcription polymerase chain reaction; WIS, Wistar; WIS-C, WIS rats with standard diet; WIS-S, WIS rats with salsalate-containing diet; mRNA, messenger RNA.
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f7-dmso-7-381: Expression of genes reflecting inflammation in liver tissue with salsalate treatment.Notes: (A) Ifit1 and (B) Iigp1 mRNA measured by qRTPCR in liver tissue samples taken at sacrifice from GK and WIS rats treated with and without salsalate treatment. Histograms represent means and error bars one standard deviation of the mean. **P<0.01.Abbreviations: GK, Goto-Kakizaki; GK-C, GK rats with standard diet; GK-S, GK rats with salsalate-containing diet; qRTPCR, quantitative reverse transcription polymerase chain reaction; WIS, Wistar; WIS-C, WIS rats with standard diet; WIS-S, WIS rats with salsalate-containing diet; mRNA, messenger RNA.

Mentions: Our previous studies on GK animals entailed microarray analyses of liver, adipose tissue, and skeletal muscle.21–23 We further examined two genes, both related in some way to inflammatory processes and previously identified as differentially regulated in all three tissues during the entire disease progression time course in our array studies. We developed specific and highly quantitative qRTPCR assays for both genes, and compared their expression in liver, adipose tissue, and muscle taken from all four groups of animals. The Ifit1 and Iigp1 expressions were significantly higher in all three tissues from untreated GK animals compared to WIS controls (Figures 6–8). The qRTPCR analyses in non-salsalate-treated GK rats from this study are consistent with results from our previous microarray studies.21–23 This suggests that heightened inflammation is present in GK rats. In adipose tissue, salsalate significantly decreased mRNA expression of Ifit1 and Iigp1 in GK animals (Figure 6), indicating that salsalate impacts the inflammation-related gene expression in adipose tissue. However, there was no therapeutic effect of salsalate shown in liver and muscle tissues from GK animals (Figures 7 and 8). In contrast, expression of Ifit1 mRNA in liver tissue of GK-S animals was higher than that in the GK-C group.


Diabetes disease progression in Goto-Kakizaki rats: effects of salsalate treatment.

Wang X, DuBois DC, Cao Y, Jusko WJ, Almon RR - Diabetes Metab Syndr Obes (2014)

Expression of genes reflecting inflammation in liver tissue with salsalate treatment.Notes: (A) Ifit1 and (B) Iigp1 mRNA measured by qRTPCR in liver tissue samples taken at sacrifice from GK and WIS rats treated with and without salsalate treatment. Histograms represent means and error bars one standard deviation of the mean. **P<0.01.Abbreviations: GK, Goto-Kakizaki; GK-C, GK rats with standard diet; GK-S, GK rats with salsalate-containing diet; qRTPCR, quantitative reverse transcription polymerase chain reaction; WIS, Wistar; WIS-C, WIS rats with standard diet; WIS-S, WIS rats with salsalate-containing diet; mRNA, messenger RNA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128793&req=5

f7-dmso-7-381: Expression of genes reflecting inflammation in liver tissue with salsalate treatment.Notes: (A) Ifit1 and (B) Iigp1 mRNA measured by qRTPCR in liver tissue samples taken at sacrifice from GK and WIS rats treated with and without salsalate treatment. Histograms represent means and error bars one standard deviation of the mean. **P<0.01.Abbreviations: GK, Goto-Kakizaki; GK-C, GK rats with standard diet; GK-S, GK rats with salsalate-containing diet; qRTPCR, quantitative reverse transcription polymerase chain reaction; WIS, Wistar; WIS-C, WIS rats with standard diet; WIS-S, WIS rats with salsalate-containing diet; mRNA, messenger RNA.
Mentions: Our previous studies on GK animals entailed microarray analyses of liver, adipose tissue, and skeletal muscle.21–23 We further examined two genes, both related in some way to inflammatory processes and previously identified as differentially regulated in all three tissues during the entire disease progression time course in our array studies. We developed specific and highly quantitative qRTPCR assays for both genes, and compared their expression in liver, adipose tissue, and muscle taken from all four groups of animals. The Ifit1 and Iigp1 expressions were significantly higher in all three tissues from untreated GK animals compared to WIS controls (Figures 6–8). The qRTPCR analyses in non-salsalate-treated GK rats from this study are consistent with results from our previous microarray studies.21–23 This suggests that heightened inflammation is present in GK rats. In adipose tissue, salsalate significantly decreased mRNA expression of Ifit1 and Iigp1 in GK animals (Figure 6), indicating that salsalate impacts the inflammation-related gene expression in adipose tissue. However, there was no therapeutic effect of salsalate shown in liver and muscle tissues from GK animals (Figures 7 and 8). In contrast, expression of Ifit1 mRNA in liver tissue of GK-S animals was higher than that in the GK-C group.

Bottom Line: While this difference in blood glucose between 4 and 21 weeks in GK-S animals was significant, blood glucose at 21 weeks was significantly lower in GK-S compared to GK-C animals.At sacrifice, salsalate decreased plasma insulin (GK-S =1.0±0.3; GK-C =2.0±0.3 ng/mL, P<0.001) and increased plasma adiponectin concentrations (GK-S =15.9±0.7; GK-C =9.7±2.0 μg/mL, P<0.001).These results suggest that salsalate acts to both increase adiponectin and decrease adipose tissue-based inflammation while preventing type 2 diabetes disease progression in GK rats.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.

ABSTRACT
This study investigates the antidiabetic effects of salsalate on disease progression of diabetes in non-obese diabetic Goto-Kakizaki (GK) rats, an experimental model of type 2 diabetes. Salsalate was formulated in rat chow (1,000 ppm) and used to feed rats from 5 to 21 weeks of age. At 5 weeks of age, GK and Wistar (WIS) control rats were subdivided into four groups, each composed of six rats: GK rats with standard diet (GK-C); GK rats with salsalate-containing diet (GK-S); WIS rats with standard diet (WIS-C); and WIS rats with salsalate-containing diet (WIS-S). The GK-C rats (167.2±11.6 mg/dL) showed higher blood glucose concentrations than WIS-C rats (133.7±4.9 mg/dL, P<0.001) at the beginning of the experiment, and had substantially elevated blood glucose from an age of 15 weeks until sacrifice at 21 weeks (341.0±133.6 mg/dL). The GK-S rats showed an almost flat profile of blood glucose from 4 weeks (165.1±11.0 mg/dL) until sacrifice at 21 weeks of age (203.7±22.2 mg/dL). While this difference in blood glucose between 4 and 21 weeks in GK-S animals was significant, blood glucose at 21 weeks was significantly lower in GK-S compared to GK-C animals. At sacrifice, salsalate decreased plasma insulin (GK-S =1.0±0.3; GK-C =2.0±0.3 ng/mL, P<0.001) and increased plasma adiponectin concentrations (GK-S =15.9±0.7; GK-C =9.7±2.0 μg/mL, P<0.001). Salsalate also lowered total cholesterol in GK-S rats (96.1±8.5 mg/dL) compared with GK-C rats (128.0±11.4 mg/dL, P<0.001). Inflammation-related genes (Ifit1 and Iigp1) exhibited much higher mRNA expression in GK-C rats than WIS-C rats in liver, adipose, and muscle tissues, while salsalate decreased the Ifit1 and Iigp1 mRNA only in adipose tissue. These results suggest that salsalate acts to both increase adiponectin and decrease adipose tissue-based inflammation while preventing type 2 diabetes disease progression in GK rats.

No MeSH data available.


Related in: MedlinePlus