The pharmacology of the insulinomimetic effect of zinc complexes.
In developing new insulinomimetic zinc(II) complexes with different coordination structures and with a blood glucose-lowering effect to treat type 2 diabetic animals, we found a potent bis(maltolato)zinc(ll) complex, Zn(mal)(2). Using the complex as the leading compound, we examined the in vitro and in vivo structure-activity relationships of Zn(mal)(2) and its related complexes in respect to the inhibition of free fatty acids (FFA) release and the enhancement of glucose uptake in isolated rat adipocytes treated with epinephrine (adrenaline), and hypoglycemic activity. Among the compounds tested, a new Zn(II) complex with allixin that was isolated from garlic, bis(allixinato)Zn(II), Zn(alx)(2), was found to exhibit the highest insulin-mimetic and hypoglycemic activities in type 2 KK-A(y) diabetic mice. On the basis of the results, Zn(alx)(2), complex was proposed to be a potent candidate for the treatment of type 2 diabetes.
Sakurai
Hiromu
H
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-oho, Misasagi, Japan. sakurai@mb.kyoto phu.acjp
Adachi
Yusuke
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004195:Disease Models, Animal; D004837:Epinephrine / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test; D006801:Humans; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000494:pharmacology; D013997:Time Factors; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology*
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008024:Ligands; D009942:Organometallic Compounds; D017967:Zinc Compounds; C499174:bis(allixinato)zinc; D005947:Glucose; D015032:Zinc; D004837:Epinephrine