Donut-shaped [NaP5W30O110]14- polyoxometalate as a promising antidiabetic drug-candidate: putative mechanisms of action.

Abstract

The aim of this study was to elucidate the potential mechanism of the antihyperglycemic action of the donut-shaped Preyssler-Pope-Jeannin polyanion salt (NH₄)₁₄[NaP₅W₃₀O₁₁₀] 31H₂O (NaP₅W₃₀) and its effect on metabolic disorders associated with diabetes. For this purpose, relevant parameters of blood glucose regulation, lipid profile, and electrolyte status were monitored in streptozotocin (STZ)-induced diabetic rats that were orally treated with 20 mg/kg/day NaP₅W₃₀ for three weeks. The serum insulin concentration was increased in diabetic animals treated with NaP₅W₃₀ (20 mg/kg/day, per os, three weeks), which could be one of the possible mechanisms of the confirmed antihyperglycemic effect. In addition, the administration of NaP₅W₃₀ significantly reduced hyperglycemia and glycated haemoglobin A_1c (HbA_1c) in STZ-induced diabetic rats, although normoglycemic values were not achieved. Furthermore, a statistically significant 1.3-fold reduction in serum total cholesterol and a 1.7-fold reduction in high-density lipoprotein (HDL) cholesterol were observed in the NaP₅W₃₀ treatment group compared to the diabetic control group. In contrast, NaP₅W₃₀ had no effect on homeostasis model assessment of insulin resistance (HOMA-IR) index values, electrolyte concentrations, or serum concentrations of low-density lipoprotein (LDL) cholesterol, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), or total triglycerides. In summary, NaP₅W₃₀ effectively improved glycoregulation in diabetic rats via the considerable stimulation of insulin as a putative mechanism. Moreover, NaP₅W₃₀ did not affect rat weight or disrupt lipid and electrolyte status, common diabetes-followed side effects and risk factors for various life-threatening complications. Thus, NaP₅W₃₀ could be considered a promising antidiabetic drug-candidate that deserves further investigation.