How Astragalin Modulates Glucose Uptake and Insulin Secretion in β-cell Lines

Type 2 diabetes mellitus is marked by chronic hyperglycemia and insulin resistance, leading to progressive tissue damage. Flavonoids such as astragalin have emerged as promising antidiabetic compounds. This study investigated the effects of astragalin on glucose uptake, insulin secretion and ionic mechanisms in pancreatic β-cells (MIN6 and INS-1). Glucose uptake and insulin secretion were quantified by bioluminescence and ELISA, respectively, while ionic currents were assessed by whole-cell patch clamp using selective pharmacological blockers. Astragalin progressively enhanced glucose uptake, reaching a plateau between 3 and 5 h, suggesting improved mitochondrial function and modulation of calcium- and AMPK-dependent signaling pathways. Insulin secretion was significantly stimulated after 1 h of treatment with 100 µM astragalin, involving ATP-sensitive K⁺ channels, voltage-dependent K⁺ channels, and L-type Ca²⁺ channels. Electrophysiological patch-clamp studies showed that astragalin reduces potassium channel currents, indicating partial channel closure and consequent membrane depolarization as corroborated by calcium involvement by using verapamil, an ionic environment associated with insulin exocytosis. These findings suggest that astragalin acts as a metabolic modulator and secretagogue in β-cells coupling insulin-stimulus secretion, representing a potential candidate for antidiabetic therapeutic strategies.