Heteroleptic oxidovanadium(IV)-malate complex improves glucose uptake in HepG2 and enhances insulin action in streptozotocin-induced diabetic rats.

Autor: de Nigro, Thanise Pitelli, Manica, Graciele Cristiane More, de Souza, Susan Webber, Jesus, Carlos Henrique Alves, Bottini, Rúbia Camila Ronqui, Missina, Juliana Morais, Valdameri, Glaucio, Nunes, Giovana Gioppo, da Cunha, Joice Maria, Picheth, Geraldo, Rego, Fabiane Gomes de Moraes
Zdroj: BioMetals; Oct2022, Vol. 35 Issue 5, p903-919, 17p
Abstrakt: Diabetes mellitus, a complex and heterogeneous disease associated with hyperglycemia, is a leading cause of mortality and reduces life expectancy. Vanadium complexes have been studied for the treatment of diabetes. The effect of complex [VO(bpy)(mal)]·H2O (complex A) was evaluated in a human hepatocarcinoma (HepG2) cell line and in streptozotocin (STZ)-induced diabetic male Wistar rats conditioned in seven groups with different treatments (n = 10 animals per group). Electron paramagnetic resonance and 51V NMR analyses of complex A in high-glucose Dulbecco's Modified Eagle Medium (DMEM) revealed the oxidation and hydrolysis of the oxidovanadium(IV) complex over a period of 24 h at 37 °C to give low-nuclearity vanadates "V1" (H2VO4), "V2" (H2V2O72−), and "V4" (V4O124−). In HepG2 cells, complex A exhibited low cytotoxic effects at concentrations 2.5 to 7.5 μmol L−1 (IC50 10.53 μmol L−1) and increased glucose uptake (2-NBDG) up to 93%, an effect similar to insulin. In STZ-induced diabetic rats, complex A at 10 and 30 mg kg−1 administered by oral gavage for 12 days did not affect the animals, suggesting low toxicity or metabolic impairment during the experimental period. Compared to insulin treatment alone, complex A (30 mg kg−1) in association with insulin was found to improve glycemia (30.6 ± 6.3 mmol L−1 vs. 21.1 ± 8.6 mmol L−1, respectively; p = 0.002), resulting in approximately 30% additional reduction in glycemia. The insulin-enhancing effect of complex A was associated with low toxicity and was achieved via oral administration, suggesting the potential of complex A as a promising candidate for the adjuvant treatment of diabetes. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index