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

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.

Hypoglycemic mechanisms of Polygonatum sibiricum polysaccharide in db/db mice via regulation of glycolysis/gluconeogenesis pathway and alteration of gut microbiota

“…We found both Pi3k and Akt were suppressed in db/db mice ( Fig. 2 E), consistent with previous studies [ 46 ]. However, neither Pi3k nor Akt were activated in the PP group compared to the DM group, although Akt had an upward trend ( Fig.…”

Therapeutic potential of artemisinin and its derivatives in managing kidney diseases

“…ART inhibited the production of intracellular lipids in a dose-dependent manner, decreased the levels of TG and the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A, which affected adipocyte differentiation ( Jang, 2016 ). In addition, artemether reduced TG and TC levels and the expression of FAS in db/db mice, and it increased liver lipid metabolism-related enzymes, such as PPARα, acetyl-CoA carboxylase 1, and carnitine palmitoyl transferase 1 ( Bai et al, 2020 ).…”

Artemether treatment improves islet function and metabolic homeostasis in diabetic nonhuman primates

“…In addition, we have reported that the antimalaria artemisinin drugs induced transdifferentiation of pancreatic α cells into insulin‐producing cells 9 . The therapeutic effects of artemisinins on the insulin insufficiency and metabolic disorders of rodent diabetic models, as well as the underlying mechanism, have been broadly validated in multiple independent studies 10–18 …”

“… 9 The therapeutic effects of artemisinins on the insulin insufficiency and metabolic disorders of rodent diabetic models, as well as the underlying mechanism, have been broadly validated in multiple independent studies. 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 …”

“…9 The therapeutic effects of artemisinins on the insulin insufficiency and metabolic disorders of rodent diabetic models, as well as the underlying mechanism, have been broadly validated in multiple independent studies. [10][11][12][13][14][15][16][17][18] In contrast, van der Meulen et al and Ackermann et al challenged the findings about artemisinins with several models that were not employed by the original studies. Based on the negative results derived from these studies, the authors claimed that artesunate treatment may exert no or even detrimental effects on the healthy islets of mice in vivo or ex vivo.…”