engleski

Peroxovanadium complex bpV(phen) is a potent antidiabetic agent with no cytotoxic side effects

Vanadium compounds are known for their numerous insulin-like effects: enhanced glucose transport, activation of glycolysis and glycogenesis, and depression of glycogenolysis and gluconeogenesis, but potential cytotoxic side effects seem to exclude clinical use of vanadate in humans. However, peroxovanadium compounds are potent insulinomimetic agents with great chemical stability and with bimodal effects on cells: proliferation at lower and cell death at higher micromolar concentrations. We investigated possible cytotoxicity of lower micromolar concentrations of potassium bisperoxo(1, 10-phenantroline)oxovanadate, bpV(phen) in rat insulinoma RINm5F cells, a model ; ; ; -cells. Results showed that 1 and 3 µ M cell line for pancreatic bpV(phen) induced cell proliferation both after 24 h and 48 h, as shown by MTT viability assay with absence of apoptotic changes in the chromatin integrity (Hoechst 33258 staining), when compared to untreated control cells. In order to explain these findings we studied expression and activation of MAP kinases and of MAPK phosphatase MKP-1 by Western blot analysis. BpV(phen) influenced MAPK activation and expression of MKP-1. We found strong and sustained activation of antiapoptotic ERK, what preceded enhanced cell survival. However, no activation of proapoptotic JNK and p38 MAPK was observed. We conclude that lower micromolar bpV(phen) concentrations were not cytotoxic, but rather stimulated RINm5F cell survival associated with sustained ERK activation and induction of MKP-1 expression. These results, together with findings that bpV(phen) is a potent insulinomimetic agent, could render this compound as an attractive therapeutic agent for managing diabetes mellitus.

diabetes; peroxovanadium; MAPK; apoptosis

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