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

Abstract

Vanadium compounds are known to exert insulin-enhancing activity, normalize elevated blood glucose levels in diabetic subjects, and show significant activity in models of insulin resistance (IR). Faced with insulin resistance, the present work investigates the antidiabetic performance of a known oxidovanadium(IV)-based coordination compound-[V^IVO(octd)]-and effects associated with glucocorticoid-induced insulin resistance in mice. The effects of [V^IVO(octd)] were evaluated in a female Swiss mice model of insulin resistance induced by seven days of dexamethasone treatment in comparison with groups receiving metformin treatment. Biological assays such as hematological, TyG index, hepatic lipids, glycogen, oxidative stress in the liver, and oral glucose tolerance tests were evaluated. [V^IVO(octd)] was characterized with ⁵¹V NMR, infrared spectroscopy (FTIR), electron paramagnetic resonance (EPR), electronic absorption spectroscopy, and mass spectrometry (ESI-FT-MS). The [V^IVO(octd)] oral treatment (50 mg/kg) had an antioxidant effect, reducing 50% of fast blood glucose (p < 0.05) and 25% of the TyG index, which is used to estimate insulin resistance (p < 0.05), compared with the non-treated group. The oxidovanadium-sulfur compound is a promising antihyperglycemic therapeutic, including in cases aggravated by insulin resistance induced by glucocorticoid treatment.

Keywords: diabetes mellitus; insulin resistance; vanadium complex.

Figure 1

Electronic absorption spectra of the [V^IVO(octd)] complex (2 mmol L⁻¹) in aqueous solution at different times.

Scheme 1

Chemical equation representative of the oxidation process of the complex species—[V^IVO(octd)]—and the product obtained—[V^VO₂(octd)^–].

Figure 2

Effects of [V^IVO(octd)] administration on (A) fasting blood glucose data, (B) fasting triglycerides data, and (C) TyG index in the following animal groups: control, DEXA, VO^IVVO₂₅, VO^IVVO₅₀, and DEXA Met (0, 7th and 14th days). The mean values with different superscript letters are statistically different at p < 0.05 and were analyzed using one-way ANOVA. ^a vs. control; ^b vs. DEXA group.

Figure 3

Effects of [V^IVO(octd)] administration on (A) total body weight (g), (B) food intake (mL), and (C) fluid intake (mL) after 14 days in the following animal groups: DEXA, VO^IVVO₂₅, VO^IVVO₅₀, and DEXA Met (1st to 14th days). The mean values with different superscript letters are statistically different at p < 0.05 and were analyzed using one-way ANOVA. ^a vs. control; ^b vs. DEXA group.

Figure 4

Effects of [V^IVO(octd)] administration on (A) blood glucose (0 and 120 min) and (B) AUC data of the following animal groups: DEXA, VO^IVVO₂₅, VO^IVVO₅₀, and DEXA Met. The mean values with different superscript letters are statistically different at p < 0.05 and were analyzed using one-way ANOVA. ^a vs. control; ^b vs. DEXA group.