Antihyperglycemic action of isoferulic acid in streptozotocin-induced diabetic rats

Abstract

Wistar rats with streptozotocin-induced diabetes (STZ-diabetic rats), which is similar to human insulin-dependent diabetic mellitus (IDDM), were employed to investigate the antihyperglycemic action of isoferulic acid. A single intravenous injection of isoferulic acid decreased the plasma glucose in a dose-dependent manner in the STZ-diabetic rats. Repeated intravenous administration of STZ-diabetic rats with isoferulic acid (5.0 mg kg(-1)) also resulted in the lowering of plasma glucose after one day. Stimulatory effects of isoferulic acid on the glucose uptake and glycogen synthesis in soleus muscles isolated from STZ-diabetic rats were also obtained indicating an increase of glucose utilization following isoferulic acid treatment which was not dependent on insulin. The mRNA level of glucose transporter subtype 4 form (GLUT4) in soleus muscle was raised by isoferulic acid after repeated treatment for 1 day in STZ-diabetic rats. Similar repeated treatment with isoferulic acid reversed the elevated mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) in liver of STZ-diabetic rats to the normal level. However, expression of GLUT4 and PEPCK genes in nondiabetic rats were not influenced by similar treatment with isoferulic acid. These results suggest that isoferulic acid can inhibit hepatic gluconeogenesis and/or increase the glucose utilization in peripheral tissue to lower plasma glucose in diabetic rats lacking insulin.

Figure 1

The effects of isoferulic acid on plasma glucose concentrations in STZ-diabetic rats. Values are expressed as mean±s.e.mean and were obtained from ten rats. STZ-diabetic rats treated with vehicle at the same volume were used as control (C). ^**P<0.01 vs the control.

Figure 2

Upper picture shows the representative response of the level of mRNA for GLUT4 or β-actin in soleus muscle isolated from nondiabetic or STZ-diabetic rats receiving repeated treatment with isoferulic acid (5.0 mg kg⁻¹) or the same volume of vehicle three times per day for 1 day. Lane 1, vehicle-treated nondiabetic rats (non-diabetes vehicle); lane 2, isoferulic acid-treated nondiabetic rats (non-diabetes isoferulic acid); lane 3, vehicle-treated STZ-diabetic rats (diabetes vehicle); lane 4, isoferulic acid-treated STZ-diabetic rats (diabetes isoferulic acid). Quantification of the mRNA level using the GLUT4/β-actin ratio is expressed as the mean±s.e.mean (n=4 per group) in each column is indicated in the lower picture. ^*P<0.05 vs data for the vehicle-treated nondiabetic rats.

Figure 3

Upper picture shows the representative response of the level of mRNA for PEPCK or β-actin in soleus muscle isolated from nondiabetic or STZ-diabetic rats receiving the repeat treatment with isoferulic acid (5.0 mg kg⁻¹) or the same volume of vehicle three times daily for 1 day. Lane 1, vehicle-treated nondiabetic rats (non-diabetes vehicle); lane 2, isoferulic acid-treated nondiabetic rats (non-diabetes isoferulic acid); lane 3, vehicle-treated STZ-diabetic rats (diabetes vehicle); lane 4 isoferulic acid-treated STZ-diabetic rats (diabetes isoferulic acid). Quantification of the mRNA level using the PEPCK/β-actin ratio is expressed as the mean±s.e.mean (n=4 per group) in each column is indicated in the lower picture. ^*P<0.05 vs data for the vehicle-treated nondiabetic rats.