Ultrastructural Analysis of In Vivo Hypoglycemiant Effect of Two Polyoxometalates in Rats with Streptozotocin-Induced Diabetes

Abstract

Two polyoxometalates (POMs), synthesized through a self-assembling method, were used in the treatment of streptozotocin (STZ)-induced diabetic rats. One of these nanocompounds [tris(vanadyl)-substituted tungsto-antimonate(III)-anions—POM1] was previously described in the literature, whereas the second [tris-butyltin-21-tungsto-9-antimonate(III)-anions—POM2], was prepared by us based on our original formula. In rats with STZ-induced diabetes treated with POMs (up to a cumulative dose of 4 mg/kg bodyweight at the end of the treatments), statistically significant reduced levels of blood glucose were measured after 3 weeks, as compared with the diabetic control groups (DCGs). Ultrastructural analysis of pancreatic β-cells (including the mean diameter of secretory vesicles and of their insulin granules) in the treated diabetic rats proved the POMs contribute to limitation of cellular degeneration triggered by STZ, as well as to the presence of increased amounts of insulin-containing vesicles as compared with the DCG. The two POMs also showed hepatoprotective properties when ultrastructural aspects of hepatocytes in the experimental groups of rats were studied. Based on our in vivo studies, we concluded that the two POMs tested achieved hypoglycemiant effects by preventing STZ-triggered apoptosis of pancreatic β-cells and stimulation of insulin synthesis.

In vivo toxicity evaluation of two polyoxotungstates with potential antidiabetic activity using Wistar rats as a model system

“…These ndings are in agreement with previously published similar effects obtained for the animals (rats and mice) treated with various other polyoxotungstates. 7,9,19 In addition, both studied polyoxotungstates (20 mg per kg per day, 14 days) did not affect the serum glucose concentration in the healthy rats (Fig. 3).…”

“…The obtained hypoglycemic effect of the investigated polyoxotungstates is in agreement with previously published in vivo studies that reported effective hypoglycemic actions of various types of polyoxotungstates on different diabetic animal models. [7][8][9] According to literature, a few putative mechanisms of POM induced normoglycemic action were indicated: a-glucosidase activity inhibition that consequently results in the reduced absorption of intestinal carbohydrates, 8 insulin mimetic effects including glucose uptake stimulation and lipolysis inhibition, 27 prevention of STZ-induced apoptosis of pancreatic b-cells, and stimulation of insulin synthesis. 7 Moreover, some polyoxotungstates were found to prevent the development of diabetic life-threatening microvascular and macrovascular complications by signicant limitation of aldose reductase activities and accumulation of advanced glycation end products.…”

“…6 Thus, the development of new potent and comfortable classes of blood glucose-lowering medications with minimal side effects to supplement actual therapeutics is urgently needed. Accordingly, in vivo studies [7][8][9] revealed that some polyoxometalates (POMs) induced normoglycemic effects in diabetic animal models. Therefore the investigation of POM normoglycemic properties might be a promising research direction resulting in the development of comfortable and lowcost POM-based antidiabetic drugs.…”

Vanadium in Biological Action: Chemical, Pharmacological Aspects, and Metabolic Implications in Diabetes Mellitus

“…The hypoglycemic potential of various vanadium compounds has also been examined in models that present features similar to those observed in types 1 and 2 diabetes mellitus. In models that resemble type 1 diabetes, administration of polyoxovanadates (e.g., decavanadate) improves serum glucose levels and glucose tolerance, albeit the insulin deficiency improvement has been demonstrated in a limited number of studies [92,[280][281][282][283][284][285][286]. Indeed, decavanadate has demonstrated to be more efficient than BMOV in inducing glucose uptake in rat adipocytes [287].…”

“…Therefore, in both diabetic animals and humans, the administration of vanadium decreases the hepatic glucose production [284,285,312], although discrepancies in this respect still exist [45,268,269,288,289]. Finally, the direct biochemical control of glucose homeostasis for vanadium treatments is associated with the enhancement in glycolysis and glucose oxidation as observed in isolated rat adipose tissue and hepatocytes HepG2 cells [17,281,301,313].…”