INSULIN-MIMETIC VANADYL-DITHIOCARBAMATE COMPLEXES

As candidates for insulin mimetics, we prepared five vanadyl-dithiocar bamate complexes with VO(S-4) coordination mode, and determined their structures by elemental analysis, visible absorption, IR and electron spin resonance spectra; the five complexes were bis(N,N-dimethyldithio carbamate)oxovanadium(IV) (VO-DMD), bis(N,N-diethyldithiocarbamate)oxo vanadium(IV) (VO-DED), bis(pyrrolidine-N-dithiocarbamate) oxovanadium( IV) (VO-PYD), bis hyl,N'-D-glucamine-dithiocarbamate)oxovanadium(IV) ( VO-MGD) and bis(sarcosine-N-dithiocarbamate) oxovanadium(IV) (VO-SAD). The insulin-mimetic activities were evaluated by in vitro and in vivo experiments. These complexes inhibited the release of free fatty acid (FFA) from isolated rat adipocytes, similar to the action of insulin. Among them, VO-PYD and VO-SAD complexes were found to be the most eff ective. In addition, the VO-PYD complex promoted the incorporation of glucose in rat L6 muscle cells. Based on these in vitro observations, both VO-PYD and VO-SAD complexes were given to streptozotocin-induced diabetic rats (STZ-rats) intraperitoneally or orally. Serum glucose le vels of STZ-rats dropped from hyperglycemic levels to the normal range within 1 or 2 days after both intraperitoneal and oral administration s of the complexes. To understand the insulin-mimetic action of the VO -PYD complex, the organ distribution of vanadium was investigated. In normal rats treated with VO-PYD complex, vanadium was distributed in a lmost all tissues, indicating that the action of vanadium is not perip heral. In addition, vanadium was found in bone and kidney when VO-PYD was given. On the basis of these results, the VO-PYD complex is indica ted to be a good agent to treat insulin-dependent diabetes in experime ntal animals. (C) 1998 Elsevier Science S.A. All rights reserved.