Regulatory Effects of Pumpkin Seed Extract on Glucose Metabolism and Insulin Signaling in Diabetic Models

Diabetes mellitus is a chronic metabolic disorder characterized by impaired insulin signaling and glucose homeostasis. In this study, a defatted pumpkin seed extract (PSE), prepared via supercritical fluid extraction, was investigated for its potential antidiabetic effects. In streptozotocin-induced diabetic rats, PSE supplementation significantly reduced fasting blood glucose, HbA1c (glycated hemoglobin), and fasting insulin levels and homeostasis model assessment of insulin resistance. Oral glucose tolerance tests revealed enhanced insulin sensitivity in a dose-dependent manner. RNA sequencing of insulin-resistant C2C12 myotubes revealed differentially expressed genes related to PI3K/Akt signaling and mitochondrial function. Western blot analysis further demonstrated increased phosphorylation of the insulin receptor and Akt, suggesting the PSE-mediated activation of insulin signaling in skeletal muscle. These preclinical findings warrant further clinical and safety evaluation of PSE and PSE-02 as nutraceutical candidates.