High insulin concentrations repress insulin receptor gene expression in calf hepatocytes cultured in vitro.

The major role of insulin and the insulin receptor (InsR) in the liver is to mediate glucose uptake into hepatocytes to synthesize glycogen and to maintain blood glucose homeostasis. In this study, we investigated the effects of high insulin concentrations on InsR gene expression in calf hepatocytes cultured in vitro. After the cells were cultured for 72 h, insulin was added to the culture solution at final concentrations of 0, 1, 10, 100 or 1000 nM. InsR mRNA expression was determined by semi-quantitative RT-PCR. The results showed that InsR mRNA expression in hepatocytes, adjusted for ß-actin expression, decreased dose dependently with increasing insulin concentration. InsR mRNA expression was similar at 1 and 10 nM insulin, but was significantly lower than that in the control. InsR expression was similar at 100 and 1000 nM insulin, but was significantly lower than that in the control, 1 and 10 nM insulin groups. These data suggest that high concentrations of insulin significantly repress InsR mRNA expression in calf hepatocytes, and this inhibition occurs in a dose-dependent manner. Further studies are needed to investigate the mechanisms underlying these effects of insulin.