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1.
Oxid Med Cell Longev ; 2016: 6058705, 2016.
Article in English | MEDLINE | ID: mdl-27119007

ABSTRACT

New potential drugs based on vanadium are being developed as possible treatments for diabetes mellitus (DM) and its complications. In this regard, our working group developed metforminium decavanadate (MetfDeca), a compound with hypoglycemic and hypolipidemic properties. MetfDeca was evaluated in models of type 1 and type 2 diabetes mellitus, on male Wistar rats. Alloxan-induction was employed to produce DM1 model, while a hypercaloric-diet was employed to generate DM2 model. Two-month treatments with 3.7 µg (2.5 µM)/300 g/twice a week for DM2 and 7.18 µg (4.8 µM)/300 g/twice a week for DM1 of MetfDeca, respectively, were administered. The resulting pharmacological data showed nontoxicological effects on liver and kidney. At the same time, MetfDeca showed an improvement of carbohydrates and lipids in tissues and serum. MetfDeca treatment was better than the monotherapies with metformin for DM2 and insulin for DM1. Additionally, MetfDeca showed a protective effect on pancreatic beta cells of DM1 rats, suggesting a possible regeneration of these cells, since they recovered their insulin levels. Therefore, MetfDeca could be considered not only as an insulin-mimetic agent, but also as an insulin-enhancing agent. Efforts to elucidate the mechanism of action of this compound are now in progress.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Metformin/therapeutic use , Vanadates/therapeutic use , Animals , Diabetes Mellitus, Experimental/blood , Glucose Tolerance Test , Glycated Hemoglobin/metabolism , Glycogen/metabolism , Hyperglycemia/complications , Hyperglycemia/drug therapy , Insulin/therapeutic use , Male , Metformin/administration & dosage , Rats, Wistar , Triglycerides/blood , Vanadates/administration & dosage
2.
J Inorg Biochem ; 147: 85-92, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25920353

ABSTRACT

Because of the increasing global spread of type 2 diabetes mellitus, there is a need to develop new antidiabetic agents. Recently we have synthesized new decavanadates using metformin as counterion. In particular, the compound containing three metforminium dications has been obtained in high yield and has been completely characterized. Biological studies using Wistar rats that have been fed with a high caloric diet inducing insulin resistance and metabolic syndrome were carried out. Results of the impact on key biochemical parameters mediated by metformin alone and the new compound are here presented. The metforminium decavanadate (H2Metf)3[V10O28]·8H2O, abbreviated as Metf-V10O28, was shown to have pharmacological potential as a hypoglycemic, lipid-lowering and metabolic regulator, since the resulting compound made of the two components with antidiabetic activities, reduces both dosage and time of administration (twice a week). Hence, due to the beneficial effects induced by the metforminium decavanadate we recommend to continue the exploration into the mechanism and toxicology of this new compound.


Subject(s)
Glucose Metabolism Disorders/drug therapy , Hyperlipidemias/drug therapy , Hypoglycemic Agents/therapeutic use , Hypolipidemic Agents/therapeutic use , Metformin/analogs & derivatives , Metformin/therapeutic use , Vanadates/therapeutic use , Animals , Carbohydrate Metabolism , Diet, High-Fat/adverse effects , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacokinetics , Hypolipidemic Agents/chemical synthesis , Hypolipidemic Agents/pharmacokinetics , Lipid Metabolism , Male , Metformin/chemical synthesis , Metformin/pharmacokinetics , Rats , Rats, Wistar , Tissue Distribution , Vanadates/chemical synthesis , Vanadates/pharmacokinetics
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