The Effects of Emodin on Insulin Resistance in KKAy Mice with Diabetes Mellitus

Background: Emodin can ameliorate insulin resistance in diabetes mellitus (DM), but the molecular mechanisms are still uncertain. Objective: The objective of this study is to identify the potential molecular mechanisms of emodin‑mediated type 2 DM treatment. Methods: We treated the type 2 diabetic KKAy mice with emodin in different doses. Biochemistry data were collected, and the expression of peroxisome proliferator activated receptor γ (PPARγ) and Glucose transporter (GLUT)‑2/4 were examined in liver, muscle, and adipose tissues using immunohistochemistry and reverse transcriptase polymerase chain reaction. The expression of IRS‑1, PI3K, pAkt‑ser473, and FoxO1 were also tested in these tissues. Results: Our data demonstrated that the levels of cholesterol, higher fasting plasma glucose, total cholesterol, total triacylglycerol, low‑density lipoprotein cholesterol, free fatty acid, C creative protein, and tumor necrosis factor‑α (P < 0.05), lower high‑density lipoprotein, and insulin sensitivity index (P < 0.05) were ameliorated by emodin in a dose‑dependent manner (P < 0.05). In addition, emodin was also identified to improve insulin sensitivity in KKAy diabetic mice (P < 0.05). In DM, the expression of PPARγ and GLUT‑2 was down‑regulated in liver (P < 0.05) as well as in muscle and adipose tissues (P < 0.05) when compared with the controls. However, the decreased levels were subject to emodin treatment in a dose‑dependent manner. Meantime, emodin was identified to up‑regulate the expression of IRS‑1, PI3K, Akt‑ser473 (P < 0.05), while FoxO1 (P < 0.05) was down‑regulated. Conclusion: These results suggest that emodin represents a promising target to improve insulin sensitivity by enhancing liver glucose utilization, glucose uptake of muscle, and fat through IRS/PI3K/Akt/FoxO1 pathway.