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

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 Ca 2+ 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 Ca 2+ levels, activating CaMKII, a Ca 2+ ‐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.