Antihyperglycemic and pancreatic tissue-preserving effects of L. sativum oil in streptozotocin-induced diabetic rats: exploratory analysis of PDX-1 and GCK.

Abstract

Background: Diabetes mellitus constitutes a major global health burden. L. sativum has long been employed in traditional medicine for glycemic management, an effect attributed to its rich phytochemical constituents, including flavonoids, phenolic acids, and glucosinolates. This study investigated the ameliorative effects of L. sativum oil against streptozotocin-induced type 1 diabetes in rats, with particular emphasis on pancreatic and duodenal homeobox 1 (PDX-1) and glucokinase (GCK) gene expression.

Methods: A total of 48 young male Wistar rats were randomly divided into four experimental groups (n = 12 per group): a control group (CG), a streptozotocin-induced type 1 diabetic group (SG; 60 mg/kg, single intraperitoneal injection), a diabetic group treated with L. sativum oil group (S+LSG; 250 mg/kg/day, oral gavage), and a healthy group receiving L. sativum oil alone (LSG; 250 mg/kg/day).

Results: In this study, the SG exhibited significant hyperglycemia, hypoinsulinemia, and dyslipidemia compared to the CG (P < 0.01). Treatment of diabetic rats with L. sativum oil (S+LSG) markedly attenuated these metabolic abnormalities, lowering blood glucose to 146.33 mg/dL, raised insulin to 15.51 µIU/mL, and improving the lipid profile relative to the SG. Histological analysis indicated severe islet atrophy, extensive cytoplasmic vacuolation, and interstitial fibrosis in the SG group, while the S+LSG group displayed notable architectural improvement and preserved islet integrity. Analysis of serum oxidative stress markers revealed that the SG exhibited significantly reduced (P < 0.01) activities of glutathione (GPx), superoxide dismutase (SOD), and catalase (CAT) compared to the CG. Furthermore, treatment with L. sativum (S+LSG) significantly restored these enzyme activities to GPx, SOD, and CAT. In contrast, serum MDA levels were markedly elevated in the SG relative to the CG, and were partially reduced in the S+LSG. Gene expression analysis revealed significant downregulated in the PDX-1 (0.802-fold) and GCK (0.779-fold) in the SG compared to CG (P < 0.01). Treatment with L. sativum oil in the diabetic rats (S+LSG) resulted in partial restoration (PDX 1: 0.830-fold and GCK: 0.840-fold); however, these changes were not statistically significant relative to SG.

Conclusion: L. sativum oil may effectively alleviate hyperglycemia, preserve pancreatic tissue architecture, and enhance antioxidant defense mechanisms in streptozotocin-induced diabetic rats.