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.