Diabetes and Obesity Drug Discovery & Therapy (Track)




Fibroblast growth factor-21 ameliorates both diabetes and obesity

Deshan Li
North east Agricultural University, College of Life Science, Harbin, P.R.China

Abstract:

Most diabetic patients show dysfunctions in both glucose and lipid metabolisms. For treatment of diabetes, it is better to ameliorate both glucose and lipid dysfunctions at the same time. However, insulin only regulates glucose metabolism. Our experimental results show that fibroblast growth factor (FGF)-21 can regulate both glucose and lipid metabolisms in type 1 and 2 models, as well as obese animals.

In glucose regulation, FGF-21demonstrated two kinds of functional patterns (i.e. acute glucose, cumulative, and long lasting glucose lowering patterns). In acute action, FGF-21 could lower blood glucose in db/db type 2 diabetic mice, STZ-induced type 1 diabetic mice and rats for 2-3 hours after administration. Insulin could dramatically enhance the acute glucose lowering effect. In long lasting action, one dose of FGF-21 could maintain blood glucose level of diabetic animals for 48 hours after several administrations. This action is more obvious with type 2 diabetes model. Insulin also dramatically enhanced the efficacy of the long lasting glucose lowering function. The long lasting action resulted in deduction of the glycosylated hemaglutinin to normal level, which reflected long term blood glucose control status. Molecular studies showed that FGF-21 stimulated GLUT1 and G6P expression and enhanced liver glycogen synthesis in the experimental animals. These results supported the pharmaceutical observations.

In lipid regulation, FGF-21 significantly reduced body weight of both mouse and rat obese models after administration of FGF-21 for one month without changing the food intake. Postmortem studies showed no visible pathological and histological lesion except 52% deduction of abdominal fat. Blood chemistry studies showed that both blood TG and LDL level of the experimental animals were significantly reduced. In contrast, blood HDL level of the model rodents was significantly elevated. Molecular basis of lipid metabolism was also explored.