Antidiabetic Effect of Artemether in Db/Db Mice Involves Regulation of AMPK and PI3K/Akt Pathways

Front Endocrinol (Lausanne). 2020 Sep 25:11:568864. doi: 10.3389/fendo.2020.568864. eCollection 2020.

Abstract

The traditional Chinese medicine has long been used in the treatment of diabetes, one major disease threatening the public health. It has been reported that artemether exerts antidiabetic effects on type 2 diabetes in db/db mice, however the underlying mechanisms remain unknown. In the present study, we show that artemether regulates expression of related enzymes participating in the glucose and lipid metabolism in the liver of db/db mice, which could at least partly explain the improved glucose and lipid metabolism in artemether-treated mice. Additionally, artemether also regulates expression of glycogen synthesis related enzymes in the skeletal muscle of db/db mice, supporting its promotive role in glycogen synthesis. Mechanistically, artemether activates AMPK pathway as well as PI3K/Akt pathway in the liver and skeletal muscle of db/db mice, suggesting that these two signaling pathways are both involved in the antidiabetic effects of artemether on type 2 diabetes in db/db mice. In conclusion, our study connects the antidiabetic effects of artemether to the regulation of metabolic enzymes and signaling pathways, and also provides molecular basis for the potential application of artemether in treating type 2 diabetes.

Keywords: AMPK; Db/db mouse; PI3K/Akt 3; artemether; type 2 diabetes.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Artemether / pharmacology
  • Artemether / therapeutic use*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / blood*
  • Diabetes Mellitus, Experimental / drug therapy
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Random Allocation
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Artemether
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases