Biomolecules & Therapeutics
Effects of the Combination of Evogliptin and Leucine on Insulin Resistance and Hepatic Steatosis in High-Fat Diet-Fed Mice
Chang Yell Shin, Hak Yeong Lee, Gil Hyung Kim, Sun Young Park, Won Seok Choi and Uy Dong Sohn*
Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul 06974, Republic of Korea
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Received: January 6, 2021; Revised: February 9, 2021; Accepted: February 27, 2021; Published online: April 5, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

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In this study, we aimed to investigate the effects of 8 weeks of treatment with a combination of evogliptin and leucine, a branchedchain 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: Evogliptin, Leucine, High-fat diet, Insulin resistance

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