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-A y Mice

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) ]) was recently reported to be a potent anti-DM candidate. We examined the effects of [Zn(hkt) ] 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) ] administration experiments in KK-A mice as a type 2 DM animal model. Ingestion of [Zn(hkt) ] resulted in lower blood glucose levels compared with the non-treated KK-A mice (control group). Additionally, [Zn(hkt) ] treatment decreased plasma insulin concentration compared with that of the non-treated KK-A group. [Zn(hkt) ] 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-A control group. The [Zn(hkt) ] 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-A control group. However, the Zn level in the pancreas of the [Zn(hkt) ] treatment group did not show the significant increase compared with the non-treated KK-A control group. This accumulation of Zn in pancreas suggested that [Zn(hkt) ] mainly effects on the peripheral tissue, and [Zn(hkt) ] has the less effect on the pancreas directly. Thus, we concluded that [Zn(hkt) ] exerted the main effect on peripheral organs by ameliorating insulin resistance.