α-Amyrin induces GLUT4 translocation mediated by AMPK and PPARδ/γ in C2C12 myoblasts. 2021

Abraham Giacoman-Martínez, and Francisco Javier Alarcón-Aguilar, and Alejandro Zamilpa, and Fengyang Huang, and Rodrigo Romero-Nava, and Rubén Román-Ramos, and Julio César Almanza-Pérez
Laboratorio de Farmacología, Departamento de Ciencias de la Salud, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de México, México.

α-Amyrin, a natural pentacyclic triterpene, has an antihyperglycemic effect in mice and dual PPARδ/γ action in 3T3-L1 adipocytes, and potential in the control of type 2 diabetes (T2D). About 80% of glucose uptake occurs in skeletal muscle cells, playing a significant role in insulin resistance (IR) and T2D. Peroxisome-proliferator activated receptors (PPARs), in particular PPARδ and PPARγ, are involved in the regulation of lipids and carbohydrates and, along with adenosine-monophosphate (AMP) - activated protein kinase (AMPK) and protein kinase B (Akt), are implicated in translocation of glucose transporter 4 (GLUT4); however, it is still unknown whether α-amyrin can affect these pathways in skeletal muscle cells. Our objective was to determine the action of α-amyrin in PPARδ, PPARγ, AMPK, and Akt in C2C12 myoblasts. The expression of PPARδ, PPARγ, fatty acid transporter protein (FATP), and GLUT4 was quantified using reverse transcription quantitative PCR and Western blot. α-Amyrin increased these markers along with phospho-AMPK (p-AMPK) but not p-Akt. Molecular docking showed that α-amyrin acts as an AMPK-allosteric activator, and may be related to GLUT4 translocation, as evidenced by confocal microscopy. These data support that α-amyrin could have an insulin-mimetic action in C2C12 myoblasts and should be considered as a bioactive molecule for new multitarget drugs with utility in T2D and other metabolic diseases.

UI MeSH Term Description Entries
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D047494 PPAR delta A nuclear transcription factor. It is activated by PROSTACYCLIN. PPARdelta,PPARD protein,Peroxisome Proliferator-Activated Receptor delta,Peroxisome Proliferator Activated Receptor delta
D047495 PPAR gamma A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS. PPARgamma,PPARgamma2,PPARgamma3,Peroxisome Proliferator-Activated Receptor gamma,Thiazolidinedione Receptor,mPPARgamma1,mPPARgamma2,Peroxisome Proliferator Activated Receptor gamma,Receptor, Thiazolidinedione
D050612 Fatty Acid Transport Proteins A broad category of membrane transport proteins that specifically transport FREE FATTY ACIDS across cellular membranes. They play an important role in LIPID METABOLISM in CELLS that utilize free fatty acids as an energy source. Fatty Acid-Transport Protein,Fatty Acid Transport Protein
D051275 Glucose Transporter Type 4 A glucose transport protein found in mature MUSCLE CELLS and ADIPOCYTES. It promotes transport of glucose from the BLOOD into target TISSUES. The inactive form of the protein is localized in CYTOPLASMIC VESICLES. In response to INSULIN, it is translocated to the PLASMA MEMBRANE where it facilitates glucose uptake. GLUT-4 Protein,GLUT4 Protein,Insulin-Responsive Glucose Transporter,SLC2A4 Protein,Solute Carrier Family 2, Facilitated Glucose Transporter, Member 4 Protein,GLUT 4 Protein,Glucose Transporter, Insulin-Responsive,Insulin Responsive Glucose Transporter
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053978 Pentacyclic Triterpenes Five-ring derivatives of dammarane having a chair-chair-chair-boat configuration. They include the lupanes, oleananes, amyrins, GLYCYRRHIZIC ACID, and soyasaponins. Adianane Derivatives,Adiananes,Baccharane Triterpenes,Fernane Derivatives,Fernanes,Gammacerane Derivatives,Gammaceranes,Hopane Derivatives,Hopanes,Hopenoid Derivatives,Pentacyclic Triterpenoids,Triterpenes, Pentacyclic,Triterpenes, Baccharane
D055372 AMP-Activated Protein Kinases Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP. 5'-AMP-Activated Protein Kinase,AMP-Activated Kinase,AMP-Activated Protein Kinase,AMP-Activated Protein Kinase alpha Subunit,AMP-Activated Protein Kinase alpha Subunits,AMP-Activated Protein Kinase beta Subunit,AMP-Activated Protein Kinase beta Subunits,AMP-Activated Protein Kinase gamma Subunit,AMP-Activated Protein Kinase gamma Subunits,PRKAA,5' AMP Activated Protein Kinase,AMP Activated Kinase,AMP Activated Protein Kinase,AMP Activated Protein Kinase alpha Subunit,AMP Activated Protein Kinase alpha Subunits,AMP Activated Protein Kinase beta Subunit,AMP Activated Protein Kinase beta Subunits,AMP Activated Protein Kinase gamma Subunit,AMP Activated Protein Kinase gamma Subunits,AMP Activated Protein Kinases
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking

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