High-fat Diet and Low-dose Streptozotocin-Induced Type 2 Diabetes: In Silico and in Vivo Study of Heterocyclic Derivatives

Abstract

Aim: The present study aimed to design and evaluate novel heterocyclic derivatives for their antidiabetic potential
using in silico molecular docking and in vivo evaluation in a high-fat diet (HFD) and low-dose streptozotocin
(STZ)–induced type 2 diabetic rat model. Material and Methods: In silico molecular docking was performed to
assess the binding affinity and interaction patterns of the heterocyclic derivatives with the dipeptidyl peptidase-4
(DPP-4) enzyme. For in vivo evaluation, type 2 diabetes mellitus (T2DM) was induced in rats by feeding an
HFD followed by administration of low-dose STZ. Antidiabetic activity was assessed using fasting blood glucose
levels and oral glucose tolerance test (OGTT). Results and Discussion: Molecular docking studies revealed
strong binding interactions of selected heterocyclic derivatives with key active-site residues of the DPP-4 enzyme.
In vivo studies demonstrated a significant reduction in fasting blood glucose levels and a marked improvement in
glucose tolerance in treated groups compared with diabetic control animals. Conclusion: The combined in silico
and in vivo findings indicate that the designed heterocyclic derivatives exhibit promising antidiabetic activity
in the HFD/STZ-induced type 2 diabetes model and may serve as potential lead compounds for further drug
development.