Synthetic multinuclear chromium assembly activates insulin receptor kinase activity: Functional model for low-molecular-weight chromium-binding substance

The biologically-active form of chromium, low-molecular-weight chromium-binding substance (LMWCr), activates the insulin-dependent tyrosine protein kinase activity of insulin receptor (IR). The site of activation was shown to be on the active site fragment of the beta subunit of IR. As LMWCr previously has been proposed to contain a multinuclear chromic assembly, the ability of multinuclear chromium assemblies to activate IR kinase activity has been probed. The trinuclear cation [Cr3O(O2CCH2CH3)(6)(H2O)(3)](+) (1) has been found to activate IR activity in a fashion almost identical to that of LMWCr using rat adipocytic membrane fragments and an active site fragment of IR, while a variety of other chromic complexes have in contrast been found to be ineffective or to inhibit kinase activity. The activation of IR kinase activity by complex 1, its stability in aqueous and strongly acidic solution, and its low molecular weight suggest that it potentially could be used in a treatment for adult-onset diabetes.