Antidiabetic zinc(II)-N-acetyl-L-cysteine complex: evaluations of in vitro insulinomimetic and in vivo blood glucose-lowering activities.
The diabetic state is known to induce oxidative stress in its mechanism, which in turn is responsible for the complications of diabetes mellitus (DM). Recently, we found that Zn(II) complexes have in vitro insulinomimetic and in vivo blood glucose-lowering activities. During our study on the development of new Zn(II) complexes with antioxidative ligands involving L-cysteine, L-cysteine-methylester, and N-acetyl-L-cysteine (nac), we found a new (N-acetyl-L-cysteinato)Zn(II) (Zn(nac)) complex by evaluating of both its in vitro insulinomimetic and in vivo potencies. The insulinomimetic activity of Zn(nac) with respect to the inhibition of free fatty acid release in isolated rat adipocytes treated with epinephrine was higher than that of a well-known insulinomimetic VOSO4, being equivalent to that of ZnSO4. The blood glucose level of hyperglycemic KK-Ay mice with type 2 DM was reduced by daily intraperitoneal injections of Zn(nac) for 28 days. Their serum insulin, HbA1c, TCHO, and UN levels were remarkably decreased, indicating that Zn(nac) improved the insulin resistance of the mice. The improvement of DM by Zn(nac) was also confirmed by the oral glucose tolerance test. In conclusion, Zn(nac) complex is proposed to attenuate both hyperglycemia and hyperinsulinemia in KK-Ay mice by decreasing serum insulin, HbA1c, UN, and TCHO levels.
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan.
Yusuke
Y
Adachi
Yutaka
Y
Yoshikawa
Hiromu
H
Sakurai
D000111:Acetylcysteine / Q000737:chemistry* / Q000494:pharmacology*; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005951:Glucose Tolerance Test; D006454:Hemoglobins / Q000187:drug effects; D006943:Hyperglycemia / Q000188:drug therapy; D006946:Hyperinsulinism / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc
D000975:Antioxidants; D001786:Blood Glucose; D006454:Hemoglobins; D007004:Hypoglycemic Agents; D007328:Insulin; D002784:Cholesterol; D015032:Zinc; D000111:Acetylcysteine