The effects of KTO-7924, a beta3-adrenergic receptor agonist, on improvement of diabetic pathology in Zucker diabetic fatty rats.

Abstract

Background and Aims.

It is reported that beta3 adrenergic receptor agonists showed the improvement of lipid metabolism and diabetes in rodent diabetes model. It is thought that beta 3 adrenergic receptor agonists increased lipolysis and induction of uncoupling protein 1 in adipose tissue, which induced hypertrophic adipose cells convert into small adipose cells. The present study intended to demonstrate effects of KTO-7924 on Zucker diabetic fatty rats.

Methods.

The Zucker diabetic fatty rats were assigned control group and KTO-7924 treatment group (30 mg/kg twice a day for 28 days). Plasma glucose, insulin, triglyceride, free fatty acids, adiponectin were determined and oral glucose tolerance test was conducted. Organ tissues weight were measured and determined mRNA expression of adiponectin receptor 1 and adiponectin receptor 2.

Results.

In plasma glucose levels, there is clear tendency of decreasing glucose levels in  KTO-7924. In plasma insulin levels, there is tendency of remaining insulin levels at 28 days in KTO-7924. In plasma TG and FFA levels, KTO-7924 showed that those levels were decreased significantly at 7 days and maintained significant decrease until 28 days. In plasma adiponectin levels, KTO-7924 increased adiponectin levels higher significantly than control group for all 28 days. Insulin sensitivity of KTO-7924 treatment group was ameliorated significantly from oral glucose tolerance test. The mRNA expression of adiponectin receptor 2 in soleus muscle of the KTO-7924 treatment group was significantly lower than that of the vehicle control group.

Conclusion

KTO-7924 improved pathology of diabetes in Zucker diabetic fatty rats accompanying by amelioration of lipid metabolism and adipose tissue weight loss, gain of muscle weight , decrease of adiponectin receptor 2 expression in muscle.