Evaluation of the Antidiabetic potential of quercetin-3-O-β-Dglucoside in insulin-resistant 3T3-L1 adipocytes cells through modulation of glucose uptake and AMPK signaling

Abstract

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia, insulin resistance, oxidative stress, and inflammatory dysregulation. Adipose tissue dysfunction plays a major role in the progression of insulin resistance by impairing glucose uptake and metabolic homeostasis. The present study investigated the antidiabetic potential of quercetin-3-O-β-D-glucoside (isoquercitrin) in high glucose-induced insulin-resistant 3T3-L1 adipocytes, with emphasis on glucose uptake and AMPK-associated signaling pathways. Insulin resistance was induced in differentiated 3T3-L1 adipocytes under high glucose conditions, followed by treatment with isoquercitrin and metformin as the positive control. The effects of isoquercitrin were evaluated through assessment of glycogen content, antioxidant biomarkers (GPx and CAT), inflammatory mediators (NF-κB, TNF-α, and IL-6), and mRNA expression of GLUT-4, PPAR-γ, AMPK, and adiponectin. High glucose exposure significantly reduced glycogen accumulation, antioxidant enzyme levels, and expression of GLUT-4, PPAR-γ, AMPK, and adiponectin, while markedly increasing NF-κB, TNF-α, and IL-6 levels. Treatment with isoquercitrin significantly reversed these alterations in a dose-dependent manner, with the 50 μM treatment demonstrating effects comparable to metformin. Isoquercitrin restored antioxidant defense systems, suppressed inflammatory signaling, enhanced glycogen synthesis, and improved insulin-sensitive gene expression associated with glucose uptake and metabolic regulation. The findings suggest that quercetin-3-O-β-D-glucoside ameliorates insulin resistance in adipocytes through modulation of oxidative stress, inflammatory pathways, and AMPK-associated metabolic signaling. Therefore, isoquercitrin may serve as a promising natural therapeutic candidate for the management of insulin resistance and type 2 diabetes mellitus.