Background: Adenosine A1 receptor (A1-AR) activation can lower plasma glucose in diabetic rats lacking insulin. We investigated the change in A1-AR gene expression in diabetic rats.
Methods: The incorporation of [U-(14)C]-glucose into glycogen was carried out to evaluate the effect of N(6)-cyclopentyladenosine (CPA) on glucose utilization in vitro. The plasma glucose concentration was assessed by the glucose oxidase method. The mRNA and protein levels of A1-AR in isolated liver were detected by Western blotting analysis and Northern blotting analysis, respectively.
Results: The effect of CPA, an agonist of A1-AR, on glycogen incorporation in hepatocytes isolated from streptozotocin-induced diabetic rats (STZ-diabetic rats) was more marked than that from the normal rats. However, similar glycogen synthesis was not modified by 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, in the isolated hepatocytes from both the normal and the STZ-diabetic rats. A change in response at the receptor level can thus be considered. The mean level of liver mRNA transcripts encoding A1-AR was increased in STZ-diabetic rats to about 250% of that in normal rats. Exogenous insulin at a dose sufficient to normalize the plasma glucose of STZ-diabetic rats reversed the mRNA level of A1-AR in the liver after a four-day treatment. Similar results were also observed in STZ-diabetic rats that received treatment with phlorizin for four days. Moreover, the protein level of A1-AR was higher in the liver of STZ-diabetic rats than that in the normal rats. Similar treatment with exogenous insulin or phlorizin reversed the elevated protein level of A1-AR in the liver of STZ-diabetic rats to near the normal level. Therefore, correction of hyperglycemia in STZ-diabetic rats can reverse the higher gene expression of A1-AR in liver.
Conclusions: The obtained results suggest that an increase in plasma glucose is responsible for the higher gene expression of A1-AR in the liver of STZ-diabetic rats.
Copyright 2003 John Wiley & Sons, Ltd.