Effects of some Vanadyl coordination compounds on the in vitro insulin release from rat pancreatic islets

Many lines of evidence indicate that vanadium inorganic salts possess insulin-mimetic and insulinotropic properties. However, they are poorly absorbed, so high oral doses are required to achieve effective plasma concentrations with possible undesirable toxic side-effects ensuing. Various organically-chelated vanadium compounds have been synthesized that are more potent than inorganic vanadium salts in their insulin-like effects due to their greater bioavailability. Unfortunately, little is known about the possible insulin secretagogue action of organic vanadyl coordination compounds. Hence, we investigated the effect of [VO(metformin) 2 ]H 2 O, [VO(salicylidene-ethylenedimmine) 2 ] and [VO(pyrrolidine-N-dithiocarbamate) 2 ](VODTC) on insulin release from isolated rat pancreatic islets, and compared it to that of vanadyl sulfate (VOSO 4 ). Of the three coordination compounds, only VODTC was found to exert insulin secretagogue action. VODTC, within concentrations ranging from 0.1 to 1.0 mM, enhanced both basal and glucose (11 mM)-stimulated insulin release. The effect involves calcium channels, since it was not appreciable in Ca 2 + -free medium. The stimulating action of VODTC required the presence of the whole metal-chelator complex inasmuch as the chelator DTC alone was ineffective. VOSO 4 was unable to bring about any significant rise in insulin release from isolated islets. Taken together, our findings indicate that VODTC may be considered a potential elective pharmaceutical tool in the therapy of diabetes, especially of type 2, through its concomitant stimulatory effect on insulin secretion and insulin-mimetic action.