Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Effects of the Combination of Evogliptin and Leucine on Insulin Resistance and Hepatic Steatosis in High-Fat Diet-Fed Mice

  • Shin, Chang Yell (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Lee, Hak Yeong (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Kim, Gil Hyung (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Park, Sun Young (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Choi, Won Seok (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
  • Received : 2021.01.06
  • Accepted : 2021.02.27
  • Published : 2021.07.01
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Abstract

In this study, we aimed to investigate the effects of 8 weeks of treatment with a combination of evogliptin and leucine, a branched-chain amino acid, in mice with high-fat diet (HFD)-induced diabetes. Treatment with evogliptin alone or in combination with leucine reduced the body weight of the mice, compared to the case for those from the HFD control group. Long-term treatment with evogliptin alone or in combination with leucine resulted in a significant reduction in glucose intolerance; however, leucine alone did not affect postprandial glucose control, compared to the case for the mice from the HFD control group. Furthermore, the combination of evogliptin and leucine prevented HFD-induced insulin resistance, which was associated with improved homeostasis model assessment for insulin resistance, accompanied by markedly reduced liver fat deposition, hepatic triglyceride content, and plasma alanine aminotransferase levels. The combination of evogliptin and leucine increased the gene expression levels of hepatic peroxisome proliferator-activated receptor alpha, whereas those of the sterol regulatory element-binding protein 1 and stearoyl-CoA desaturase 1 were not altered, compared to the case in the HFD-fed mice (p<0.05). Thus, our results suggest that the combination of evogliptin and leucine may be beneficial for treating patients with type 2 diabetes and hepatic steatosis; however, further studies are needed to delineate the molecular mechanisms underlying the action of this combination.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology [Grant NRF-2019R1F1A1062070].

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