Fimasartan Ameliorates Deteriorations in Glucose Metabolism in a High Glucose State by Regulating Skeletal Muscle and Liver Cells

• Published in: Yonsei medical journal Vol. 63; no. 6; pp. 530 - 538
• Main Authors: Jang, Yoo Na, Lee, Yong Jik, Han, Yoon Mi, Kim, Hyun Min, Seo, Hong Seog, Jeong, Ji Hoon, Park, Seung Yeon, Jung, Tae Woo
• Format: Journal Article
• Language: English
• Published: Korea (South) Yonsei University College of Medicine 01-06-2022; 연세대학교의과대학
• Subjects: Adenosine Triphosphate - metabolism; Animals; Biphenyl Compounds; Glucose - metabolism; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 - pharmacology; Humans; Liver - metabolism; Mice; Muscle, Skeletal; Original; PPAR delta - metabolism; PPAR delta - pharmacology; Pyrimidines; Tetrazoles; 의학일반; Fimasartan; glucose metabolism; angiotensin II type 1 receptor blocker; PPARδ
• ISSN: 0513-5796; 1976-2437
• DOI: 10.3349/ymj.2022.63.6.530

Since diabetes and hypertension frequently occur together, it is thought that these conditions may have a common pathogenesis. This study was designed to evaluate the anti-diabetic function of the anti-hypertensive drug fimasartan on C2C12 mouse skeletal muscle and HepG2 human liver cells in a high glucose state.
The anti-diabetic effects and mechanism of fimasartan were identified using Western blot, glucose uptake tests, oxygen consumption rate (OCR) analysis, adenosine 5'-triphosphate (ATP) enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining for diabetic biomarkers in C2C12 cells. Protein biomarkers for glycogenolysis and glycogenesis were evaluated by Western blotting and ELISA in HepG2 cells.
The protein levels of phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), p-AKT, insulin receptor substrate-1 (IRS-1), and glucose transporter type 4 (Glut4) were elevated in C2C12 cells treated with fimasartan. These increases were reversed by peroxisome proliferator-activated receptor delta (PPARδ) antagonist. ATP, OCR, and glucose uptake were increased in cells treated with 200 µM fimasartan. Protein levels of glycogen phosphorylase, glucose synthase, phosphorylated glycogen synthase, and glycogen synthase kinase-3 (GSK-3) were decreased in HepG2 cells treated with fimasartan. However, these effects were reversed following the addition of the PPARδ antagonist GSK0660.
In conclusion, fimasartan ameliorates deteriorations in glucose metabolism as a result of a high glucose state by regulating PPARδ in skeletal muscle and liver cells.