Bis(α-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.

Potentiation of adipogenesis and insulinomimetic effects of novel vanadium complex (N'-[(E)-(5-bromo-2-oxophenyl)methylidene]-4-methoxybenzohydrazide)oxido(1,10-phenanthroline)vanadium(IV) in 3T3-L1 cells

“…Bis(allixinato) oxovanadium(IV) stimulates the translocation of GLUT4 to the plasma membrane in 3T3-L1 adipocytes following the activation of tyrosine phosphorylation of the insulin receptor beta-subunit (IR) and insulin receptor substrate (IRS) as well as Akt kinase [17]. Similar targets were identified for bis(alpha-furancarboxylato)oxovanadium(IV) (BFOV)-enhanced expression of IRS-1 and GLUT4 mRNA, which can explain the improvement of dexamethasone-induced insulin resistance in 3T3-L1 adipocytes [18]. Bis(acetylacetonato)-oxovanadium(IV) (VO(acac), bis(maltolato)-oxovanadium(IV) (BMOV), and sodium metavanadate (NaVO 3 ) attenuated lipolysis, and both Akt and ERK pathways were activated by these compounds; however, only Akt activation contributes to the antilipolytic effect of the vanadium compounds, without the involvement of ERK activation [19].…”

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

“…We have reported a new orally active antidiabetic vanadyl complex, bis (a‐furancarboxylato) oxovanadium (IV) (BFOV), which displayed a potent antidiabetic potential both in type 1 and type 2 diabetic animals in our previous studies 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 dexamethasone‐induced 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 high‐fat diet‐induced obese animal model.…”