Increase in adenosine A1 receptor gene expression in the liver of streptozotocin-induced diabetic rats.
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.
Liu
I M
IM
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan 70101, Republic of China.
Tzeng
T F
TF
Tsai
C C
CC
Lai
T Y
TY
Chang
C T
CT
Cheng
J T
JT
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000503:physiopathology*; D008112:Liver Glycogen / Q000096:biosynthesis; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000235:genetics*; D012016:Reference Values; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D058906:Purinergic P1 Receptor Agonists; D043682:Receptor, Adenosine A1; C048599:N(6)-cyclopentyladenosine; D005947:Glucose; D000241:Adenosine; D013755:Tetradecanoylphorbol Acetate