Endocrine Abstracts

Background: Diabetes mellitus type 2 (T2D) is a prevalent metabolic disorder characterized by insulin resistance and high blood sugar levels. Existing treatments focus on managing these symptoms, but there is an ongoing need for more effective interventions. Our study explores the potential of 2′,3,3,5′-Tetramethyl-4′-nitro-2′H-1,3′-bipyrazole (TMNB) in this context, based on its presumed impact on oxidation, glycation, and insulin resistance processes.

Aims/Purpose: The primary objective of this research was to investigate the efficacy of TMNB as an intervention for T2D. We aimed to understand its effects on insulin sensitivity, blood glucose levels, and molecular pathways involved in glucose metabolism.

Methods: Our study employed both in vitro and in vivo models. We induced T2D traits in mice using a high-fat diet (HFD) and streptozotocin (STZ) injections. These mice were then treated with TMNB at a dosage of 10 mg/kg daily for 12 weeks. Parallel to this, in vitro experiments were conducted using HepG2 cells, a human liver cell line integral to glucose metabolism, to assess the impact of TMNB on oxidative and glycative stresses.

Results: in vitro studies revealed that TMNB significantly reduced oxidative and glycative stresses in HepG2 cells, leading to increased insulin sensitivity. In the in vivo mouse model, TMNB treatment resulted in a decrease in fasting glucose levels and an improvement in insulin responsiveness. At the molecular level, TMNB was observed to activate phosphoglycerate kinase 1 (PGK1), enhancing the AKT signaling pathway, which is crucial for glucose uptake and counteracting insulin resistance.

Conclusion: Our findings suggest that TMNB holds significant potential as a therapeutic agent for managing T2D, primarily through its action on PGK1 and the AKT signaling pathway, highlighting the importance of targeting molecular pathways to improve glucose metabolism and insulin sensitivity.