Praecitrullus fistulosus Extract Exhibits Antidiabetic Potential by Augmenting Insulin-Signaling Cascade, GLUT-4 and IRS-1, in Streptozotocin–Nicotinamide-Induced Diabetic Rats

Diabetes mellitus is largely driven by oxidative stress that disrupts insulin signaling, leading to failure in insulin-mediated glucose absorption. Exploration of natural bioactive compounds is fueled by their promising role in correcting redox imbalance. This study aims to investigate the antidiabetic effect of the methanolic extract of <i>Praecitrullus fistulosus</i>, potentially by transcriptional modulation in streptozotocin-nicotinamide-induced diabetic rats. Male Wistar albino rats (<i>n</i> = 36) were assigned to six groups: normal control; diabetic control; standard drug group; and three treatment groups receiving <i>P. fistulosus</i> extract orally at doses of 200, 400, and 600 mg/kg body weight, respectively, for 30 consecutive days. Diabetes was induced in all groups, except for normal control, by intraperitoneal co-administration of streptozotocin and nicotinamide. Nicotinamide (100 mg/kg) was injected 15 min prior to a single dose of streptozotocin (50 mg/kg). Baseline and endpoint assessments of weight and blood glucose levels were performed. Blood was processed to assess insulin-related indices, lipid profile, and oxidative stress markers. q-PCR and Western blotting were utilized to explore the underlying molecular mechanisms. The diabetic control-group rats exhibited impaired glucose tolerance due to the marked reduction in serum insulin levels, compromised β-cell function, and substantial rise in lipid profile and oxidative stress parameters. Oral administration of <i>P. fistulosus</i> methanolic extract effectively mitigated these alterations in a dose-dependent manner, accompanied by the upregulation of both gene and protein expression involved in the insulin-signaling cascade.