Garcinia Cambogia Improves High‐Fat Diet‐Induced Glucose Imbalance by Enhancing Calcium/CaMKII/AMPK/GLUT4‐Mediated Glucose Uptake in Skeletal Muscle

• Published in: Molecular nutrition & food research Vol. 66; no. 10; pp. e2100669 - n/a
• Main Authors: Han, Joo‐Hui, Kim, Min‐Tae, Myung, Chang‐Seon
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.05.2022
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Ca2+/calmodulin-dependent protein kinase II; calcium; Calcium (intracellular); Calcium - metabolism; Calcium influx; Calcium ions; Calcium, Dietary - pharmacology; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; CaMKII; Diabetes; Diabetes mellitus; Diabetes Mellitus - metabolism; Diet; Diet, High-Fat - adverse effects; Garcinia cambogia; Garcinia cambogia - metabolism; Glucose; Glucose - metabolism; Glucose tolerance; Glucose Transporter Type 4 - metabolism; glucose uptake; High fat diet; Homeostasis; Intracellular; Intracellular signalling; MAP kinase; Mice; Muscle Fibers, Skeletal; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Myotubes; Obesity; Obesity - drug therapy; Obesity - etiology; Obesity - metabolism; Phosphorylation; Quadriceps muscle; Signal transduction; Signaling; Skeletal muscle; Translocation; AMPK; CaMKII; calcium; glucose uptake; Garcinia cambogia; diabetes
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.202100669

Scope Garcinia cambogia (G. cambogia) is known to have antiobesity effects. In this study, the therapeutic effects of G. cambogia on glucose homeostasis in obesity‐induced diabetes are explored and the underlying mechanisms are investigated. Methods and results C2C12 myotubes are treated with G. cambogia; glucose uptake, intracellular Ca2+ levels, and related alterations in signaling pathways are examined. High‐fat diet (HFD)‐fed mice are administered G. cambogia for 8 weeks; oral glucose tolerance is evaluated, and the regulation of identified targets of signaling pathways in quadriceps skeletal muscle are examined in vivo. G. cambogia increases glucose uptake in C2C12 myotubes and induces the upregulation of AMPK, ACC, and p38 MAPK phosphorylation. Notably, G. cambogia markedly elevates both intracellular Ca2+ levels, activating CaMKII, a Ca2+‐sensing protein, and TBC1D4‐mediated GLUT4 translocation, to facilitate glucose uptake. Furthermore, high‐glucose‐induced inhibition of glucose uptake and signal transduction is reverted by G. cambogia. In an HFD‐induced diabetes mouse model, G. cambogia administration results in significant blood glucose‐lowering effects, which are attributed to the regulation of targets that have been identified in vitro, in quadricep skeletal muscle. Conclusion These findings provide new insights into the mechanism by which G. cambogia regulates glucose homeostasis in obesity‐induced diabetes. Proposed mechanism of the therapeutic effect of Garcinia cambogia against obesity‐induced diabetes. G. cambogia inhibits HFD‐induced hyperglycemia by activating the Ca2+/CaMKII/AMPK/p38/TBC1D4 signaling pathway and GLUT4 translocation in skeletal muscle cells, leading to glucose uptake and homeostasis.