Antidiabetic Activity of Zn(II) Complexes with a Derivative of <scp>l</scp>-Glutamine

Abstract

Abstract The insulinomimetic activity of zinc(II) complexes Zn(gln-m)2 and Zn(gln-e)2, respectively, with l-γ-glutamyl-methylamide (gln-m) and -ethylamide (theanine: gln-e), components of green tea, were compared to that of Zn(gln)2 with l-glutamine (gln) in an in vitro study using isolated rodent adipocytes treated with epinephrine in the presence of glucose, expressed as the IC50 value (50% inhibition concentration) of free fatty acids (FFA) released from fat cells. The former were found to have higher inslinomimetic activity than that of the latter. The IC50 values of the former were 0.61 and 0.56, respectively. Then, the anti-diabetic activity of a zinc(II) complex, Zn(gln-e)2, was examined in an in vivo experiment on KK-Ay mice, model animals of type-2 DM, by the intraperitoneal (ip) injection of 3–4 mg Zn/kg b.w./day for 13 days. The blood-glucose level of a group treated with a Zn complex, Zn(gln-e)2, decreased significantly after 13 days compared to those of non-treated and gln-e treated groups. The serum concentrations of triglyceride (TG) and HbA1c decreased significantly in Zn(gln-e)2 treated KK-Ay mice compared to those of the gln-e treated group, respectively. Furthermore, the improvement in glucose tolerance was confirmed by an oral glucose tolerance test.