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

Mol Nutr Food Res. 2022 May;66(10):e2100669. doi: 10.1002/mnfr.202100669. Epub 2022 Mar 6.


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.

Keywords: AMPK; CaMKII; Garcinia cambogia; calcium; diabetes; glucose uptake.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Calcium / metabolism
  • Calcium, Dietary / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Diabetes Mellitus* / metabolism
  • Diet, High-Fat / adverse effects
  • Garcinia cambogia / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Glucose* / metabolism
  • Mice
  • Muscle Fibers, Skeletal
  • Muscle, Skeletal / metabolism
  • Obesity / drug therapy
  • Obesity / etiology
  • Obesity / metabolism


  • Calcium, Dietary
  • Glucose Transporter Type 4
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • AMP-Activated Protein Kinases
  • Glucose
  • Calcium