Cucurbitane Triterpenoids from the Fruits of Momordica Charantia Improve Insulin Sensitivity and Glucose Homeostasis in Streptozotocin‐Induced Diabetic Mice

Scope Momordica charantia (M. charantia) has antidiabetic effects, and cucurbitane‐type triterpenoid is one of the compounds of M. charantia. This study aims to investigate whether the new cucurbitane‐type triterpenoids affect insulin sensitivity both in vitro and in vivo, and the underlying mechanisms. Methods and results Four compounds (C1–C4) isolated from the ethanol extract of M. charantia enhance glucose uptake in C2C12 myotubes via insulin receptor substrate‐1 (IRS‐1) rather than via adenosine monophosphate‐activated protein kinase. The most potent, compound 2 (C2), significantly increases the activation of IRS‐1 and downstream signaling pathways, resulting in glucose transporter 4 translocation. Furthermore, these C2‐induced in vitro effects are blocked by specific signal inhibitors. We further evaluate the antidiabetic effect of C2 using a streptozotocin (STZ)‐induced diabetic mouse model. Consistent with in vitro data, treatment with C2 (1.68 mg kg–1) significantly decreases blood glucose level and enhances glycogen storage in STZ‐injected mice. These effects appear to be mediated by the IRS‐1 signaling pathway in skeletal muscle, not in adipose and liver tissues, suggesting that C2 improves hyperglycemia by increasing glucose uptake into skeletal muscle. Conclusion Our findings demonstrate that the new cucurbitane‐type triterpenoids have potential for prevention and management of diabetes by improving insulin sensitivity and glucose homeostasis.