Abstract
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.