Mn(II)-Mediated Self-Assembly of Tea Polysaccharide Nanoparticles and Their Functional Role in Mice with Type 2 Diabetes

Tea polysaccharide (TPS) is a bioactive compound that has attracted increasing attention for its health effect on regulating the metabolism of glucose and lipid. Moreover, due to their good biocompatibility and biodegradability, TPS-based nanoparticles have emerged as effective nanocarriers for the delivery of bioactive molecules. In this study, we developed a TPS-based biocarrier system for the orally targeted administration of Mn(II) ions and investigated their antidiabetic effects in C57BL/6 mice with HFD/streptozotocin (STZ)-induced T2DM. Mn(II)-loaded TPS-based nanoparticles (MTNPs) were synthesized, in which negatively charged functional groups in protein and uronic acid in TPS conjugates would act as binding sites for Mn(II) ions, which is responsible for the cross-linking reaction of MTNP. The resulting MTNP had a spherical shape and a mean particle size of around 30 nm with a Mn(II) ion content of 2.24 ± 0.13 mg/g. In T2DM mice, we discovered that MTNP treatment significantly lowered blood glucose levels and improved glucose intolerance. Furthermore, the impact of MTNP on the recovery of FINS, the homeostatic index of insulin resistance (HOMA-IR), and the homeostatic index of β-cell (HOMA β-cell) levels was significantly larger (p < 0.05) than TPS alone, demonstrating that Mn(II) ions can enhance TPS’s ability to repair HFD/STZ-induced β-cell damage. Mn(II) ions in MTNP not only acted as cofactors to increase the exocytosis of insulin secretory cells by upregulating the expression of Ca(II)/calmodulin-dependent protein kinase II (CaMK II) but also promoted TPS’s lipid-lowering effect in T2DM mice by inhibiting glucogenesis and regulating the lipid metabolism. Our findings suggest that Mn(II) ions can be used not only as cross-linkers in the formation of nanoparticulated TPS but also as cofactors in improving the functional role of TPS in regulating the glucose and lipid metabolism, which will provide insights into the development of TPS-based drug delivery systems for the prevention of type 2 diabetes.