Zanthoxylum alkylamides activate phosphorylated AMPK and ameliorate glycolipid metabolism in the streptozotocin-induced diabetic rats

ABSTRACT

This study aimed to evaluate the effects of Zanthoxylum alkylamides on the glycolipid metabolism of rats with streptozotocin (STZ)-induced diabetes. Diabetic rats were given daily oral treatments of 2, 4, or 8 mg/kg bw alkylamides for 28 days. Alkylamides significantly decreased fasting blood glucose and fructosamine content, as well as relieved organ enlargement caused by diabetes. The serum and liver triglyceride, malondialdehyde, and free fatty-acid contents of rats with STZ-induced diabetes were significantly reduced. Total cholesterol in the liver also significantly decreased. Quantitative polymerase chain reaction (Q-PCR) and Western blot detected insignificantly increased (P > 0.05) mRNA expression levels of adenosine monophosphate-activated protein kinase (AMPK) in the skeletal muscle of diabetic rats. However, AMPK and p-AMPK (Thr172) protein expression levels significantly increased. The mRNA and protein expression levels of silencing information regulator 1 significantly increased. The mRNA expression levels of acetyl-CoA-carboxylase (ACC) and protein p-ACC (Ser79) also increased. The mRNA and protein expression levels of glucose transporter type 4 (GLUT4) were significantly upregulated in the skeletal muscle cell membranes of diabetic rats. Results indicated that alkylamides activated the AMPK-signaling pathway. Thus, inhibiting ACC activity reduced fatty-acid synthesis. The rapid translocation of GLUT4 mediated increased glucose transport rate and reduced blood glucose. Therefore, alkylamides can ameliorate glucose and lipid metabolism disorders in diabetic rats by activating the AMPK pathway.

KEYWORDS:

• AMPK
• diabetes
• glycolipid metabolism
• rat
• Zanthoxylum alkylamides

Conflicts of interest

The authors declare no financial conflict of interest.

Funding

This work was supported by the National Natural Science Foundation of China (NSFC 31371834), the Basis and Frontline of Research Project in Chongqing of China (cstc2014jcyjA10073) and Southwest University Courtyard Level Projects (2015).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (NSFC 31371834), the Basis and Frontline of Research Project in Chongqing of China (cstc2014jcyjA10073) and Southwest University Courtyard Level Projects (2015).

Notes on contributors

Tingyuan Ren

T. Y. Ren and J. Q. Kan conceived and designed the study; T. Y. Ren and Y. P. Zhu were involved in the study concept and design, and in drafting the manuscript.

Yuping Zhu

T. Y. Ren and J. Q. Kan conceived and designed the study; T. Y. Ren and Y. P. Zhu were involved in the study concept and design, and in drafting the manuscript.