Investigation of a CuII-poly(γ-glutamic acid) complex in aqueous solution and its insulin-mimetic activity

The complexation between cupric ions (Cu-II) and poly(gamma-glutamic acid) (gamma-PGA) in aqueous solutions (pH 3-11) has been studied by UV-visible absorption and electron spin resonance (ESR) techniques. Formation of the Cu-II-gamma-PGA complex is confirmed by the observation of the blue shift of the absorption band in the visible region, anisotropic line shapes in the ESR spectrum at room temperature, and a computer simulation of the visible absorption spectrum of the complex. The structure of the Cu-II-gamma-PGA complex, depending on the pH, has been determined. The in vitro insulin-mimetic activity of the Cu-II-gamma-PGA complex is examined by determining both inhibition of free fatty acid release and glucose uptake in isolated rat adipocytes treated with 4 epinephrine, in which the concentration of the Cu-II-gamma-PGA complex for 50% inhibition of free fatty acid release is very similar to that Of CuSO4. However, it is significantly lower than that of a previously reported insulin-mimetic bis(3-hydroxypicolinato)copper(II), [Cu(3hpic)(2)], complex.