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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

Plasma insulin with salsalate treatment.Notes: Insulin concentrations in plasma taken at sacrifice measured by enzyme-linked immunosorbent assay. 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; WIS, Wistar; WIS-C, WIS rats with standard diet; WIS-S, WIS rats with salsalate-containing diet.
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f3-dmso-7-381: Plasma insulin with salsalate treatment.Notes: Insulin concentrations in plasma taken at sacrifice measured by enzyme-linked immunosorbent assay. 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; WIS, Wistar; WIS-C, WIS rats with standard diet; WIS-S, WIS rats with salsalate-containing diet.

Mentions: Untreated GK rats, which were 4 weeks old at the beginning of the experiment, showed mild hyperglycemia (167.2±11.6 mg/dL) that slowly progressed until 14 weeks old, indicating that disease was extant before 4 weeks of age. This observation is in agreement with previous report that T2D is evident in GK rats before birth.20 The blood glucose concentrations of GK-C rats substantially increased at 14 to 15 weeks and finally reached a plateau at around 18 weeks of age. Blood glucose concentrations of GK-C rats were significantly higher than WIS rats throughout the study (P<0.001). The concentrations of blood glucose in these four groups of animals have been previously published and well characterized by a disease progression model.24 The profile of the blood glucose concentrations in WIS-C, GK-S, and GK-C are illustrated in Figure 2. No significant differences were observed between WIS-C and WIS-S in blood glucose at any age, and their profiles were essentially superimposable. Although blood glucose concentrations of GK-S rats were still significantly higher than WIS rats, salsalate inhibited the continuous rise of blood glucose that occurred in non-drug-treated GKs and resulted in an essentially flat glucose profile in GK-S animals. As a consequence, blood glucose in GK-S rats was significantly lower (P<0.05) than in GK-C rats from 18 weeks of age onward. Plasma insulin concentrations were significantly lower in salsalate-treated rats at sacrifice (Figure 3), regardless of strain (GK-S =1.0±0.3; WIS-S =1.1±0.3; GK-C =2.0±0.3; WIS-C =1.9±0.3). These results suggest that salsalate enhanced insulin sensitivity.


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)

Plasma insulin with salsalate treatment.Notes: Insulin concentrations in plasma taken at sacrifice measured by enzyme-linked immunosorbent assay. 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; WIS, Wistar; WIS-C, WIS rats with standard diet; WIS-S, WIS rats with salsalate-containing diet.
© Copyright Policy
Related In: Results  -  Collection

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

f3-dmso-7-381: Plasma insulin with salsalate treatment.Notes: Insulin concentrations in plasma taken at sacrifice measured by enzyme-linked immunosorbent assay. 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; WIS, Wistar; WIS-C, WIS rats with standard diet; WIS-S, WIS rats with salsalate-containing diet.
Mentions: Untreated GK rats, which were 4 weeks old at the beginning of the experiment, showed mild hyperglycemia (167.2±11.6 mg/dL) that slowly progressed until 14 weeks old, indicating that disease was extant before 4 weeks of age. This observation is in agreement with previous report that T2D is evident in GK rats before birth.20 The blood glucose concentrations of GK-C rats substantially increased at 14 to 15 weeks and finally reached a plateau at around 18 weeks of age. Blood glucose concentrations of GK-C rats were significantly higher than WIS rats throughout the study (P<0.001). The concentrations of blood glucose in these four groups of animals have been previously published and well characterized by a disease progression model.24 The profile of the blood glucose concentrations in WIS-C, GK-S, and GK-C are illustrated in Figure 2. No significant differences were observed between WIS-C and WIS-S in blood glucose at any age, and their profiles were essentially superimposable. Although blood glucose concentrations of GK-S rats were still significantly higher than WIS rats, salsalate inhibited the continuous rise of blood glucose that occurred in non-drug-treated GKs and resulted in an essentially flat glucose profile in GK-S animals. As a consequence, blood glucose in GK-S rats was significantly lower (P<0.05) than in GK-C rats from 18 weeks of age onward. Plasma insulin concentrations were significantly lower in salsalate-treated rats at sacrifice (Figure 3), regardless of strain (GK-S =1.0±0.3; WIS-S =1.1±0.3; GK-C =2.0±0.3; WIS-C =1.9±0.3). These results suggest that salsalate enhanced insulin sensitivity.

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