High-intensity interval training increases AMPK and GLUT4 expressions via FGF21 in skeletal muscles of diabetic rats

Neng Tine Kartinah, Hardiyanti Rusli, Ermita I. Ibrahim Ilyas, Trinovita Andraini, Nurul Paramita, Dewi Irawati S. Santoso, Brilliant Cahya Puspasari, Julfiana Mardhatillah

Research output: Contribution to journalArticlepeer-review


In type 2 diabetes, a decrease in expression of glucose transporter type 4 (GLUT4) results in decreased glucose uptake while fibroblast growth factor 21 (FGF21) promotes glucose ICLE uptake. The liver and other organs, such as the muscles, produce FGF21. Physical activity increases FGF21 secretion from skeletal muscles. FGF21 is thought to promote glucose uptake during exercise by activating AMP-activated protein kinase (AMPK). Thus, the goal of this study is to determine how high-intensity interval training (HIIT) affects glucose uptake via FGF21 signaling in diabetic rats. Twenty-four eight-week-old male Wistar rats were randomly divided into four categories including Control (Con), DM intervention (ConDM), DM group undergoing continuous training (DM-CT), and DM group undergoing high-intensity interval training (DM-HIIT). The trainings in the exercise groups (DM-CT and DM-HIIT) were performed six days a week for six weeks. We analyzed FGF21 levels in serum and muscles by ELISA. Measurement of phosphorylated AMPK in muscles used ELISA, and that of mRNA GLUT4 expression used RT-PCR. Following HIIT interventions, the glucose level in plasma was closer to normal level. An increase in FGF21 levels aided in the reduction in blood glucose. The HIIT group had significantly higher FGF21 levels in serum and muscles. An increase in FGF21 was followed by an increase in AMPK phosphorylation and GLUT4 expression in the HIIT group. In diabetic rats, HIIT promotes glucose uptake via FGF21, which activates AMPK and increases GLUT4 expression.

Original languageEnglish
Pages (from-to)136-146
Number of pages11
JournalJournal of Advanced Biotechnology and Experimental Therapeutics
Issue number1
Publication statusPublished - 2024


  • AMPK
  • Diabetes Mellitus
  • EGF21
  • Exercise
  • GLUT4
  • High-intensity interval training


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