title: Anti-hyperglycemic Effect of Long-Term Bis(hinokitiolato)zinc Complex ([Zn(hkt)2]) Ingestion on Insulin Resistance and Pancreatic Islet Cells Protection in Type 2 Diabetic KK-AyMice.
abstract: Zinc (Zn) is a trace element with anti-diabetes mellitus (anti-DM) effects. Zn complexes exhibit stronger insulin-like activity than Zn ions. Bis(hinokitiolato)zinc complex ([Zn(hkt)2]) was recently reported to be a potent anti-DM candidate. We examined the effects of [Zn(hkt)2] on insulin resistance and pancreatic islet cells through in vivo long-term ingestion studies. In an in vivo study, we performed 4-month long-term [Zn(hkt)2] administration experiments in KK-Aymice as a type 2 DM animal model. Ingestion of [Zn(hkt)2] resulted in lower blood glucose levels compared with the non-treated KK-Aymice (control group). Additionally, [Zn(hkt)2] treatment decreased plasma insulin concentration compared with that of the non-treated KK-Aygroup. [Zn(hkt)2] treatment resulted in a significant suppression of islet cell enlargement and a significantly decreased number of insulin-positive cells compared with the non-treated KK-Aycontrol group. The [Zn(hkt)2] treatment group showed the increasing tendency in the amount of Zn levels in peripheral organs; liver, muscle, adipose, and pancreas, compared with the non-treated KK-Aycontrol group. However, the Zn level in the pancreas of the [Zn(hkt)2] treatment group did not show the significant increase compared with the non-treated KK-Aycontrol group. This accumulation of Zn in pancreas suggested that [Zn(hkt)2] mainly effects on the peripheral tissue, and [Zn(hkt)2] has the less effect on the pancreas directly. Thus, we concluded that [Zn(hkt)2] exerted the main effect on peripheral organs by ameliorating insulin resistance.
authors.affiliation: Department of Analytical & Bioinorganic Chemistry, Division of Analytical & Physical Sciences, Kyoto Pharmaceutical University.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Naito
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Michiko
authors.initials: M
authors.lastname: Shintani
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamoshida
authors.forename: Naemi
authors.initials: N
authors.lastname: Kajiwara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008815:Mice, Inbred Strains; D039821:Monoterpenes / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D014131:Trace Elements / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D014334:Tropolone / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D015032:Zinc / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D017967:Zinc Compounds / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D039821:Monoterpenes; D014131:Trace Elements; D017967:Zinc Compounds; D014334:Tropolone; D015032:Zinc; C009479:beta-thujaplicin