Investigation of a Cu(II)-poly(gamma-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 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.
Karmaker
Subarna
S
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Saha
Tapan K
TK
Sakurai
Hiromu
H
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D019327:Copper Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin; D008297:Male; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D003300:Copper; D019327:Copper Sulfate