Korea University · Biochemistry, Genetics and Molecular Biology
Professor Hyeon Soo Kim's research lab specializes in cellular metabolism and signaling pathways, with a primary focus on the role of AMP-activated protein kinase (AMPK) in regulating glucose homeostasis, insulin sensitivity, and muscle function. The lab investigates myokines—such as irisin, meteorin-like protein (Metrnl), and other endogenous factors released from skeletal muscle—exploring their metabolic and anti-inflammatory effects. Using in vitro and in vivo models, the lab examines how natural compounds (e.g., quercetin, curcumin, retinoic acid) and drugs (e.g., metformin) modulate AMPK and downstream targets like p38 MAPK, PAK, HDAC5, and FoxO3a to influence glucose uptake, apoptosis, and muscle atrophy. The overarching goal is to uncover novel therapeutic targets for metabolic diseases such as type 2 diabetes and sarcopenia.
Figures are computed from collected data and may differ slightly.
Irisin is a novel myokine produced by skeletal muscle. However, its metabolic role is poorly understood. In the present study, irisin induced glucose uptake in differentiated skeletal muscle cells. It increased AMP-activated protein kinase (AMPK) phosphorylation and the inhibition of AMPK blocked glucose uptake. It also increased reactive oxygen species (ROS) generation. N-acetyl cysteine, a ROS scavenger, blocked irisin-induced AMPK phosphorylation. Moreover, irisin activated p38 MAPK in an AMP
Retinoic acid (RA) is one of the major components of vitamin A. In the present study, we found that retinoic acid activated AMP-activated protein kinase (AMPK). RA induced Rac1-GTP formation and phosphorylation of its downstream target, p21-activated kinase (PAK), whereas the inhibition of AMPK blocked RA-induced Rac1 activation. Moreover, cofilin, an actin polymerization regulator, was activated when incubated with RA. We then showed that inhibition of AMPK by compound C, a selective inhibitor
Quercetin, an anti-oxidant flavonoid that is widely distributed in the plant kingdom, has been suggested to have chemopreventive effects on cancer cells, although the mechanism is not completely understood. In this study, we found that quercetin increased the phosphorylation of AMP-activated protein kinase (AMPK) and downstream acetyl-CoA carboxylase (ACC) and suppressed the viability of HeLa cells. AICAR, an AMPK activator, and quercetin down-regulated heat shock protein (HSP)70 and increased t
Our results demonstrate that metformin treatment impairs muscle function through the regulation of myostatin in skeletal muscle cells via AMPK-FoxO3a-HDAC6 axis. The muscle-wasting effect of metformin is more evident in WT than in db/db mice, indicating that more complicated mechanisms may be involved in metformin-mediated muscular dysfunction.
Curcumin has been shown to exert a variety of beneficial human health effects. However, mechanisms by which curcumin acts are poorly understood. In this study, we report that curcumin activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. In addition, curcumin activated the mitogen-activated protein kinase kinase (MEK)3/6-p38 mitogen-activated protein kinase (MAPK) signaling pathways in the downstream of the AMPK cascade. Moreover, inhibition of either AMP
Meteorin-like (metrnl) is a recently identified adipomyokine that beneficially affects glucose metabolism; however, its underlying mechanism of action is not completely understood. We here show that the level of metrnl increases in vitro under electrical pulse stimulation and in vivo in exercised mice, suggesting that metrnl is secreted during muscle contractions. In addition, metrnl increases glucose uptake via the calcium-dependent AMPKα2 pathway in skeletal muscle cells and increases the phos
Metformin is a major oral anti-diabetic drug and is known as an insulin sensitizer. However, the mechanism by which metformin acts is unclear. In this study, we found that AICAR, an AMPK activator, and metformin increased the expression of Rab4 mRNA and protein levels in skeletal muscle C2C12 cells. The promoter activity of Rab4 was increased by metformin in an AMPK-dependent manner. Metformin stimulated the phosphorylation of AS160, Akt substrate, and Rab GTPase activating protein (GAP), and al
Insulin resistance is the primary cause responsible for type 2 diabetes. Phosphatase and tensin homolog (PTEN) plays a negative role in insulin signaling and its inhibition improves insulin sensitivity. Metformin is a widely used insulin-sensitizing drug; however, the mechanism by which metformin acts is poorly understood. To gain insight into the role of PTEN, we examined the effect of metformin on PTEN expression. Metformin suppressed the expression of PTEN in an AMP-activated protein kinase (
Docosahexaenoic acid (DHA) is an endogenous ligand of G protein-coupled receptor 120 (GPR120). However, the mechanisms underlying DHA action are poorly understood. In this study, DHA stimulated glucose uptake in the skeletal muscles in an AMP-activated protein kinase (AMPK)-dependent manner. GPR120-mediated increase in intracellular Ca(2+) was critical for DHA-mediated AMPK phosphorylation and glucose uptake. In addition, DHA stimulated GLUT4 translocation AMPK-dependently. Inhibition of AMPK an
Homocysteine sulfinic acid (HCSA) is a homologue of the amino acid cysteine and a selective metabotropic glutamate receptor (mGluR) agonist. However, the metabolic role of HCSA is poorly understood. In this study, we showed that HCSA and glutamate stimulated glucose uptake in C2C12 mouse myoblast cells and increased AMP-activated protein kinase (AMPK) phosphorylation. RT-PCR and Western blot analysis revealed that C2C12 expresses mGluR5. HCSA transiently increased the intracellular calcium conce
[6]-Gingerol has been used to control diabetes and dyslipidemia; however, its metabolic role is poorly understood. In this study, [6]-gingerol increased adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation in mouse skeletal muscle C2C12 cells. Stimulation of glucose uptake by [6]-gingerol was dependent on AMPKα2. Moreover, both Inhibition and knockdown of AMPKα2 blocked [6]-gingerol-induced glucose uptake. [6]-Gingerol significantly decreased the activity of protein phos
Inflammation is a common cause of cardiac arrhythmia. Angiotensin ІІ (Ang ІІ) is a major contributing factor in the pathogenesis of cardiac inflammation; however, its underlying molecular mechanism remains unclear. Here, we explored the effect of Ang ІІ on inflammatory mechanisms and oxidative stress using HL-1 atrial myocytes. We showed that Ang ІІ activated c-Jun N-terminal kinase (JNK) phosphorylation and other inflammatory markers, such as transforming growth factor-β1 (TGF-β1) and tumor nec
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