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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

Body weight and food intake with salsalate treatment.Note: (A) Body weights and (B) food intake normalized to body weight as a function of age in GK and WIS rats with and without salsalate treatment.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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f1-dmso-7-381: Body weight and food intake with salsalate treatment.Note: (A) Body weights and (B) food intake normalized to body weight as a function of age in GK and WIS rats with and without salsalate treatment.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: Figure 1A compares mean body weights of GK and WIS animals fed salsalate in their diet with normal-diet-fed animals throughout the course of this study. As expected, all four groups of animals exhibited continuous increases in body weights, which were almost linear up through 12 weeks of age and then tended to plateau at later ages. The GK animals were slightly heavier than WIS animals throughout; this difference was significant (P<0.01) by the end of the study. There was a trend for lower body weights in salsalate fed animals compared to the same strain not receiving salsalate. However, there is no distinct difference in food intake when normalized to body weight in any of the groups (Figure 1B). This is consistent with previous modeling efforts suggesting that reduced body weight in salsalate-treated animals results from increased metabolic rate despite similar energy intakes.24 As no obvious difference existed in normalized food intake in GK-S and WIS-S, this suggested that GK and WIS rats consumed comparable amounts of salsalate per body weight. As confirmed by high-performance liquid chromatography analyses, this produced comparable salicylic acid concentrations in the blood of GK and WIS animals fed salsalate.24


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)

Body weight and food intake with salsalate treatment.Note: (A) Body weights and (B) food intake normalized to body weight as a function of age in GK and WIS rats with and without salsalate treatment.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

f1-dmso-7-381: Body weight and food intake with salsalate treatment.Note: (A) Body weights and (B) food intake normalized to body weight as a function of age in GK and WIS rats with and without salsalate treatment.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: Figure 1A compares mean body weights of GK and WIS animals fed salsalate in their diet with normal-diet-fed animals throughout the course of this study. As expected, all four groups of animals exhibited continuous increases in body weights, which were almost linear up through 12 weeks of age and then tended to plateau at later ages. The GK animals were slightly heavier than WIS animals throughout; this difference was significant (P<0.01) by the end of the study. There was a trend for lower body weights in salsalate fed animals compared to the same strain not receiving salsalate. However, there is no distinct difference in food intake when normalized to body weight in any of the groups (Figure 1B). This is consistent with previous modeling efforts suggesting that reduced body weight in salsalate-treated animals results from increased metabolic rate despite similar energy intakes.24 As no obvious difference existed in normalized food intake in GK-S and WIS-S, this suggested that GK and WIS rats consumed comparable amounts of salsalate per body weight. As confirmed by high-performance liquid chromatography analyses, this produced comparable salicylic acid concentrations in the blood of GK and WIS animals fed salsalate.24

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