Oral administration of Adiponectin-receptor agonistic dipeptide, Tyr-Pro, prevents the onset of diabetes in Spontaneously Diabetic Torii rats

Abstract

Purpose: In our previous study, we found a dipeptide, Tyr-Pro (YP) as a natural AdipoR agonist. The aim of this study is to investigate the anti-diabetic effect of oral administration of YP in spontaneously diabetic Torii (SDT) rats.

Methods: 16-week-old (wk) male SDT rats were divided into the control, YP, and PY groups (1 mg/kg/day), administrated orally for 13 weeks.

Results: At >19 wk, weight loss and overeating, which are typical phenomena for SDT rats, were observed in the control and PY group, whereas there were no changes in the YP group. Fasting BGL in the control group increased to 142 ± 13 mg/dL at 29-wk. In contrast, fasting BGL in the YP group remained in the normal range (82-99.3 mg/dL) throughout the treatment period. At 22 wk, pre-diabetic stage, only the intake of YP improved impaired glucose tolerance by OGTT (p<0.05). The expression of AdipoR1 and p-AMPK/AMPK in skeletal muscle in the YP group was significantly higher than that of control, suggesting that YP intake has an anti-diabetic effect via AdipoR1/AMPK signaling.In conclusion, the present study demonstrates the in vivo anti-diabetic effects of the oral administration of YP as an AdipoR1 agonist.