title: Investigation of the insulin-like properties of zinc(II) complexes of 3-hydroxy-4-pyridinones: identification of a compound with glucose lowering effect in STZ-induced type I diabetic animals.
abstract: Results from an investigation in an in vivo model of STZ-induced diabetic rats demonstrate that compound bis(1,2-dimethyl-3-hydroxy-4(1H)-pyridinonate)zinc(II), Zn(dmpp)(2), significantly lowers the blood glucose levels of individuals, thus showing evidence of glucose lowering activity. The compound was selected from a set of eight zinc(II) complexes of 3-hydroxy-4-pyridinones with diverse lipophilicity that were prepared and characterized in our laboratory. Assessment of insulin-like activity of the complexes was firstly performed in vitro by measuring the inhibition of FFA release in isolated rat adipocytes. The results indicate that compounds bis(2-methyl-3-hydroxy-4-pyridinonate)zinc(II), Zn(mpp)(2) and Zn(dmpp)(2) display significantly higher activity than that of the respective positive control thus suggesting its selection for in vivo tests. Safety evaluation of the active zinc(II) compounds was performed in freshly isolated rat hepatocytes. The results support that cell viability is not significantly different from the control set after 1 and 2h of incubation with both zinc(II) complexes.
authors.affiliation: REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Moniz
authors.forename: M João
authors.initials: MJ
authors.lastname: Amorim
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.forename: Ana
authors.initials: A
authors.lastname: Nunes
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.forename: Carla
authors.initials: C
authors.lastname: Queirós
authors.forename: Andreia
authors.initials: A
authors.lastname: Leite
authors.forename: Paula
authors.initials: P
authors.lastname: Gameiro
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.forename: Fernando
authors.initials: F
authors.lastname: Remião
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sakurai
authors.forename: Maria
authors.initials: M
authors.lastname: Rangel
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D004355:Drug Stability; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D008297:Male; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D013311:Streptozocin; D015032:Zinc
chemical_list: D001786:Blood Glucose; D056831:Coordination Complexes; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D011728:Pyridones; C020366:3-hydroxy-4-pyridone; D013311:Streptozocin; D015032:Zinc