Abstract
The aim of the present study was to investigate the effects of germacrone (GM) and dexmedetomidine (DEX) in treating type 2 diabetes mellitus (T2DM). A high-fat diet (HFD)-induced T2DM rat model was established. The experimental rats were divided into the control group, HFD group, GM treatment group, DEX treatment group and GM + DEX treatment group. In addition, adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C (CC) was used to inhibit AMPKα1 expression. All rats received their respective treatment daily for 21 days. Blood glucose and lipid levels, apoptosis of hepatic cells, and levels of inflammatory factors and oxidative stress indicators in serum samples were evaluated. Protein expression of AMPKα1 and its downstream targets were also investigated. Results demonstrated that blood glucose concentration, blood lipid indicators (endothelin, total cholesterol, triglyceride and low density lipoprotein cholesterol), cell apoptosis in liver tissues, total oxidant status, malondialdehyde, interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1β levels in serum were increased in the high-fat group compared to the control but decreased following GM and/or DEX treatment. By contrast, high-density lipoprotein cholesterol and antioxidative stress indicator superoxide dismutase (SOD) were decreased in the high-fat group but increased following GM and/or DEX treatment. Protein expression of AMPKα1 and the catabolic genes carnitine palmitoyltransferase-1, peroxisome proliferator-activated receptor-α and acyl coenzyme A were decreased whilst anabolic genes, including sterol regulatory element binding protein-1c, fatty acid synthase and diacylglycerol acyltransferase-2, were increased in the HFD group. These effects were attenuated by GM and/or DEX treatment. AMPKα1 inhibition resulted in decreased SOD and increased cell apoptosis in liver tissues as well as increased IL-6, TNF-α and IL-1β levels compared with the HFD group. However, these effects were abolished following treatment with CC, GM and DEX together. Taken together these results indicated that GM worked synergistically with DEX to attenuate symptoms of high-fat-induced T2DM, with the effect potentially involving an increase in AMPKα1 expression.