Isorhamnetin exhibits hypoglycemic activity and targets PI3K/AKT and COX-2 pathways in type 1 diabetes.
Isorhamnetin Exhibits Hypoglycemic Activity and Targets PI3K/AKT and COX-2 Pathways in Type 1 Diabetes.
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Abstract
Isorhamnetin (ISO), a dietary O-methylated flavonol, was evaluated for hypoglycemic activity and mechanism in a streptozotocin (STZ) model of type 1 diabetes.We conducted untargeted plasma metabolomics (ESI±), network integration and docking, and measured pancreatic PI3K, phosphorylated AKT, and COX-2; INS-1βcells challenged with the PI3K inhibitor LY294002 were used to assess viability, intracellular ROS, and PI3K phosphorylation.ISO lowered fasting glycemia, increased circulating insulin, improved dyslipidemia by reducing low-density lipoprotein cholesterol (LDL-C), and preserved islet architecture. Untargeted plasma metabolomics (ESI±) indicated broad remodeling with enrichment of arachidonic-, linoleic-, starch/sucrose- and glycerophospholipid pathways. Network integration and docking prioritized targets converging on PI3K/AKT and COX-2/eicosanoid signaling. Consistently, in pancreatic tissue, ISO increased PI3K, phosphorylated AKT, and reduced COX-2. In INS-1 beta cells challenged with the PI3K inhibitor LY294002, ISO improved viability, decreased intracellular ROS, and partially restored PI3K phosphorylation at 4µM.Together, these data indicate that ISO exerts hypoglycemic effects while supportingβ-cell integrity through activation of PI3K/AKT and tempering of COX-2-linked lipid-mediator pathways. ISO therefore emerges as a food-derived adjunct candidate for autoimmune diabetes, and the work motivates targeted lipidomics and in vivo pathway interrogation in future studies.
Affiliation
Lijia Li
External References
- PubMed ID:
- 41156454
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