Cucurbitacin Augments Insulin Sensitivity and Glucose Uptake Through Translocation and Activation of Glut4 in Pi3k/Akt Signaling Pathway

Abstract

Vegetables that are generally consumed in India as one of the main components of the diet have been proven for their antidiabetic potential. Cucurbitacin is an important member of the Cucurbitaceae family and exhibit potential effects in various metabolic disorders and cancer. The aim of the present study is to investigate the effect and the mechanism of cucurbitacin on glucose uptake in an insulin target skeletal muscle and activation of PI3k/Akt signaling pathways in STZ induced diabetic animal model. STZ induced diabetic rats showed significantly elevated levels of plasma glucose, TBARS, and lipid hydroperoxides, and decreased levels of plasma insulin and enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non -enzymatic antioxidants (vitamin C, E and GSH), and impairment in insulin signaling proteins including IR, IRS-1/2, Akt, PI3K, GLUT4, and PPAR-γ proteins. The administration of cucurbitacin (5 mg/kg b.w/p.o) showed near-normalized levels of plasma glucose, lipid peroxidation products, enzymatic and non-enzymatic antioxidants and improved insulin signaling proteins. Based on the present findings, cucurbitacin improves glucose uptake by enhancing GLUT4 protein activities in skeletal muscle through PI3K/Akt and antioxidant defense in plasma and it also maintains blood glucose homeostasis.