Environmental exposure to arsenic can cause a variety of health problems. Epidemiological and experimental studies have established a diabetogenic role for arsenic, but the mechanisms responsible for arsenic-induced impairment of insulin action are unclear. MicroRNAs (miRNAs) are involved in various metabolic disorders, particularly in the development of insulin resistance. The present study investigated whether arsenite, an active form of arsenic, induces hepatic insulin resistance and the mechanisms underlying it. After male C57BL/6J mice were exposed to arsenite (0 or 20 ppm) in drinking water for 12 months, intraperitoneal glucose tolerance tests (IPGTTs) and insulin tolerance tests (ITTs) revealed an arsenite-induced glucose metabolism disorder. Hepatic glycogen levels were lower in arsenite-exposed mice. Further, for livers of mice exposed to arsenite, miR-191 levels were higher, and protein levels of insulin receptor substrate 1 (IRS1), p-IRS1, and phospho-protein kinase B (p-AKT) were lower. Further, glucose transporter 4 (GLUT4) had lower levels on the plasma membrane. For insulin-treated L-02 cells, arsenite decreased glucose consumption and glycogen levels, increased miR-191 levels, and inhibited the IRS1/AKT pathway and the translocation of GLUT4 from the cytoplasm to the plasma membrane. For insulin-treated L-02 cells, the decreases of glucose consumption, glycogen levels, GLUT4 on the plasma membrane, and p-AKT levels induced by arsenite were reversed by SC79 (agonist of AKT) and an miR-191 inhibitor; these effects caused by miR-191 inhibitor were restored by IRS1 siRNA. In insulin-treated L-02 cells, miR-191, via IRS1, was involved in the arsenite-induced decreases of glucose consumption and glycogen levels and in inhibition of the translocation of GLUT4. Thus, miR-191 blocking the translocation of GLUT4 was involved in arsenite-induced hepatic insulin resistance through inhibiting the IRS1/AKT pathway. Our study reveals a mechanism for arsenite-induced hepatic insulin resistance, which provides clues for discovering biomarkers for the development of type 2 diabetes and for prevention and treatment of arsenic poisoning.

High-performance affinity materials are highly required in the sample preparation process in mass spectrometry-based glycoproteomics studies. In this research, a novel magnetic nanofiber-based zwitterionic hydrophilic material is prepared for glycopeptide enrichment and identification. The one-dimensional hydroxyapatite nanofiber (HN) acted as the supporting substance for immobilizing both Fe₃O₄ nanoparticles and Au nanoparticles, following the surface modification with a zwitterionic tripeptide L-glutathione (GSH) via the affinity interactions between the thiol group in GSH and both Au and Fe₃O₄ to form the magHN/Au-GSH nanofiber. Owing to the unique structural features, excellent hydrophilicity, abundant zwitterionic molecules, and strong magnetic responsiveness, the as-prepared magHN/Au-GSH nanofiber possesses satisfactory specificity for glycopeptide enrichment. As a result, the magHN/Au-GSH nanofiber demonstrated great detection sensitivity (2 fmol), satisfying enrichment recovery (89.65%), large binding capacity (100 mg g⁻¹), and high enrichment selectivity (1 : 100) toward glycopeptides. Furthermore, 246 N-glycosylated peptides corresponding to 104 N-glycosylated proteins were identified from only 1 μL human serum, revealing the great potential of this affinity nanofiber for glycopeptide enrichment and glycoproteomics research.