Action Mechanism of Insulin‐Mimetic Vanadyl–Allixin Complex

Abstract

In the 21st century, there has been a dramatic worldwide increase in the prevalence of metabolic syndromes, including diabetes mellitus (DM). Several synthetic pharmaceutical agents have been developed and used for the treatment of type-2 DM; however, these compounds have several problems such as side effects, hypoglycemia, and weight gain. Therefore, new drugs are required for DM therapy. We have proposed that some vanadyl complexes function as potent insulin-mimetic and antidiabetic agents in type-1 and type-2 DM animal models. In this article, we review the possible action mechanism of insulin-mimetic and antidiabetic vanadyl complexes, focusing on a recently proposed complex, bis(allixinato)oxovanadium(IV), with respect to the insulin-signaling pathway in cultured adipocytes.

Study of the antidiabetic capacity of the VO(dmpp)2 complex

“…Thus, research has been carried out to develop VCs to be used as orally administered drugs in the treatment of DM, at an effective non toxic dose. Several VCs have been synthesized, such as bis(maltolato)oxovanadium (IV) (BMOV) [22], bis(picolinato)oxovanadium (IV), bis(allixinato)oxovanadium (IV), as well as other derivatives [23], and their antidiabetic properties have been investigated [24][25][26]. Indicators of insulin mimetism have been assessed through in vitro and ex vivo studies by measuring glucose uptake rates [27,28], inhibition of free fatty acid (FFA) release [29] and specific protein phosphorylation [8,25] induced by these VCs.…”

A new salicylic acid-derivatized kojic acid vanadyl complex: Synthesis, characterization and anti-diabetic therapeutic potential

“…The insulin-mimetic effect of vanadium compounds has been widely documented in diabetes animal models [7,27,28]. In this study, BSOV was designed to combine kojato and salicylic acid to provide a balanced lipo/hydrophilicity of the complex and a property of antioxidative activity.…”

Vanadium, Copper and Zinc in Medicine

“…In Figure 7.14a, the Cu þ2 ion is ligated by N-e of His 6 , His 13 or His 14 , the amino group on the N-terminus of the peptide and a carboxylate oxygen of Asp 1 . In the second model, Figure 7.14b, the donors are N-e of His 6 , His 13 and His 14 , and a carboxylate oxygen of Asp 1 . The reported binding constant for the Cu þ2 -Ab complex varies widely with the conditions of the study and values in the range 10 7 -10 11 M À1 have been reported, with one as high as $10 18 M À1 [71].…”

“…These residues have carboxylate groups directed into a pocket that is important for the binding of AMD3100 and its metal complexes (Figure 7.19b). In order to determine the role that ligand conformation and metal coordination geometry may play in the interaction of [Zn 2 (AMD3100)] 4þ with the CXCR4 receptor, Sadler and coworkers used [ 1 H, 15 N] and [ 1 H, 13 C] HSQC NMR spectroscopy to study the structure of the Zn þ2 complex in the presence of acetate ion, which is a good model for the carboxylate groups of Asp 171 and Asp 262 in the CXCR4 receptor site. A striking feature of the series is that the Pd þ2 complex, which can only bind the cyclam ligand in a square planar configuration, is inactive, but Zn þ2 , which can easily adopt a variety of different stereochemistries (Zn þ2 has zero CFSE), is the most active complex.…”

“…More than 80 years later, both vanadate and the related ion, vanadyl, VO 2þ (Figure 7.1), were shown to exhibit insulin-mimetic effects on the oxidation of glucose in adipocytes (fat cells) of rats [2][3][4], and sodium vanadate was found to be effective in controlling blood glucose levels and reducing cardiac decline in diabetic rats [5]. These early reports led to the synthesis and study of a large number of vanadium-based insulin-mimetic agents, a few of which are shown in Figure 7.1 [6][7][8][9][10][11][12][13][14]. One of these compounds, bis(ethylmaltolato)oxovanadium(IV), BEOV, is currently in phase II clinical trials in the United States as a potential new insulin-mimetic agent for treating diabetes.…”