Bis(<I>α</I>-furancarboxylato)oxovanadium(IV) prevents and improves dexamethasone-induced insulin resistance in 3T3-L1 adipocytes

Abstract

Previous studies showed that bis(alpha-furancarboxylato)oxovanadium(IV) (BFOV), an orally active anti-diabetic organic vanadium complex, could improve insulin resistance in animals with type 2 diabetes. The present study has been carried out to evaluate the effects of BFOV on insulin-resistant glucose metabolism using dexamethasone-treated 3T3-L1 adipocytes as an in-vitro model of insulin resistance. The results showed that BFOV, similar to vanadyl sulfate and rosiglitazone, caused a concentration-dependent increase in glucose consumption by insulin-resistant adipocytes. Moreover, BFOV enhanced the action of insulin and completely prevented the development of insulin resistance induced by dexamethasone, leading to glucose consumption equal to that by normal cells. In addition, dexamethasone reduced the mRNA expression of insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT4) in 3T3-L1 adipocytes, while BFOV normalized the expression of IRS-1 and GLUT4. These findings suggest that BFOV prevents and improves dexamethasone-induced insulin resistance in 3T3-L1 adipocytes by enhancing expression of IRS-1 and GLUT4 mRNA.

Dinuclear Oxidovanadium(IV) and Dioxidovanadium(V) Complexes of 5,5′‐Methylenebis(dibasic tridentate) Ligands: Synthesis, Spectral Characterisation, Reactivity, and Catalytic and Antiamoebic Activities

“…Metal ions are known to often accelerate drug action, and the efficacy of a therapeutic agent may be enhanced upon coordination with a metal ion 20. Vanadium complexes show a variety of biological properties, and oxidovanadium(IV) complexes have been used to prevent and improve dexamethasone‐induced insulin resistance in 3T3‐L1 adipocytes 21. These compounds have also been used in receptor‐mediated signals22 and as anticancer agents 23,24.…”

Dexamethasone-Induced Insulin Resistance Attenuation by Oral Sulfur–Oxidovanadium(IV) Complex Treatment in Mice

“…In addition, type 2 DM is characterized by peripherical IR, mainly in the liver, white adipose, and skeletal muscle tissues. There have been a few papers related to the investigation of vanadium compounds using IR models, high-fat diets, and synthetic glucocorticoids, which are the conditions that most represent type 2 diabetic patients [ 19 , 20 ].…”

“…Nonetheless, Barbera et al (2001) [ 20 ] showed that a treatment strategy based on the VOSO 4 did not block or attenuate DEXA-induced IR in rats. On the other hand, therapeutical strategies based on vanadium complexes are promising; for example, the use of the bis(alpha-furancarboxylato)oxidovanadium(IV) (BFOV) enhanced the action of insulin and completely prevented the development of insulin resistance induced by dexamethasone, modulating the gene expression of key proteins of the insulin cascade such as insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT4) in 3T3-L1 adipocytes [ 19 ]. Although we have not yet clarified the molecular mechanism involved in the anti-IR of [V IV O(octd)] complex, it is reasonable to hypothesize that this vanadium-based compound activates the insulin pathway in metabolically important tissues such as the liver and skeletal muscle, which counteracts the anti-insulin effects of dexamethasone.…”

“…It is approximately 50 to 100-fold more potent than cortisol. However, when administered in excess, DEX induces side effects such as muscle catabolism, hyperphagia, increased adiposity, dyslipidemia and hypertriacylglycerolemia, and IR in vitro and in vivo [ 10 , 15 , 16 , 17 , 18 , 19 , 20 ]. In addition, the long-term administration of DEX leads to the generation of free radicals such as superoxide, hydrogen peroxide, and hydroxyl radicals, which contribute to oxidative stress and deteriorate both insulin action and secretion, accelerating the consequent appearance of type 2 DM [ 21 ].…”

Combination of bis (α‐furancarboxylato) oxovanadium (IV) and metformin improves hepatic steatosis through down‐regulating inflammatory pathways in high‐fat diet‐induced obese C57BL/6J mice

“…15,18 BFOV reduced FFA release from isolated rat adipocytes treated with epinephrine and enhanced the uptake of 2-deoxy-D-[ 3 H]-glucose in dexamethasoneinduced insulin resistance 3T3-L1 adipocyte. 19 Because the BFOV and metformin (Met) have different roles in regulating glucose homeostasis, including improving the insulin sensitivity of adipose tissue and reducing hepatic glucose production, respectively, we hypothesized the combination of these two agents would provide a combined effect on insulin resistance and related hepatic steatosis in a highfat diet-induced obese animal model. Therefore, the present study is the first to examine the effects of combination therapy with BFOV and Met on type 2 diabetes and hepatic steatosis in high-fat diet-induced obese C57 mice (HFC57 mice).…”