International Journal of Diabetes & its Complications
ISSN: 2573-8895 | DOI: 10.64030/2573-8895
Sherif Salah Abdul Aziz, Khalid F. Kassem, Ahmed A. CC, Mohamed Sherif Salah, Hossam M. Afifi and Omar M. Hafez
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease characterized by chronic hyperglycemia, insulin resistance, progressive β-cell dysfunction, and persistent low-grade inflammation. Although current therapeutic approaches, particularly metformin, remain central to disease management, sustained metabolic control is still not consistently achieved in many patients. This highlights the need for novel treatment strategies that address not only glucose dysregulation but also the broader immunometabolic disturbances underlying disease progression. In the present study, GLX10 was evaluated in a high-fat diet/ low-dose streptozotocin (HFD/STZ) induced rat model of T2DM over a 91-day period. In vivo efficacy was assessed through serial random blood glucose measurements and oral glucose tolerance testing (OGTT), with glucose exposure quantified using the area under the curve from 0 to 120 minutes (AUC0–120) To ensure a rigorous safety assessment, histopathological and hematological evaluations were conducted in a separate cohort of six normal rats that received GLX10 administration at the start of the study for 20 days. Hematological parameters were subsequently monitored at 10-day intervals throughout the 91-day study period to capture potential time-dependent systemic effects. At study termination, animals were sacrificed, and comprehensive histopathological examination was performed. This approach enabled longitudinal evaluation of hematological changes alongside end-point tissue assessment, allowing for the characterization of potential GLX10-related toxicities independently of confounding effects associated with HFD and streptozotocin (STZ). Complementary in vitro studies in hepatic and macrophage- based systems were conducted to assess cytocompatibility, nitric oxide production, inflammatory cytokine release, and selected pathway-related signaling changes. GLX10 treatment was associated with a significant reduction in random blood glucose levels and a marked improvement in glucose tolerance compared with diabetic controls. Under the same experimental conditions, GLX10 also demonstrated greater improvement in OGTT AUC than metformin. In vitro, GLX10 preserved macrophage viability across functionally relevant concentrations while reducing nitric oxide production and suppressing IL-6 and TNF-α release. Exploratory signaling analyses further suggested modulation of NF-κB- and mTOR-related pathways.
Taken together, these findings support GLX10 as a promising investigational immunometabolic modulator with antidiabetic potential in a preclinical setting. Nevertheless, further mechanistic, pharmacological, and translational studies are required to confirm its therapeutic relevance.