Oral administration of a zinc complex improves type 2 diabetes and metabolic syndromes.
Previously, we reported that intraperitoneal injections of the Zn(II) complex (Zn(alx)(2)) with allixin, which is isolated from dry garlic, with a Zn(O(4)) coordination environment, exhibited high anti-diabetic effects in obesity-linked type 2 diabetic KKA(y) mice. However, this complex exhibited low activity when administered orally. To improve the effect of Zn(alx)(2), we prepared a novel Zn(II) complex with the allixin-derivative bis(1,6-dimethyl-3-hydroxy-5-methoxy-2-pentyl-1,4-dihydropyridine-4- thionato)Zn(II), abbreviated as Zn(II)-thioallixin-N-methyl (Zn(tanm)(2)), having a Zn(S(2)O(2)) coordination environment; this complex has extremely high in vitro insulin-like activity. Because Zn was extensively absorbed from the gastrointestinal tract when Zn(tanm)(2) was orally administered, its anti-diabetic effects were examined in KKA(y) mice. Daily oral administrations of Zn(tanm)(2) for 4 weeks in KKA(y) mice significantly improved hyperglycemia, glucose intolerance, insulin resistance, hyperleptinemia, obesity, and hypertension. Interestingly, Zn(tanm)(2) increased depressed plasma adiponectin levels in the mice. Here, we propose that Zn(tanm)(2) will be an orally active therapeutic for obesity-linked type 2 diabetes and metabolic syndromes.
Adachi
Yusuke
Y
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Yoshida
Jiro
J
Kodera
Yukihiro
Y
Kiss
Tamas
T
Jakusch
Tamas
T
Enyedy
Eva A
EA
Yoshikawa
Yutaka
Y
Sakurai
Hiromu
H
D000284:Administration, Oral; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D024821:Metabolic Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016896:Treatment Outcome; D015032:Zinc / Q000008:administration & dosage*
D015032:Zinc