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.
BACKGROUND: Adenosine A1 receptor (A1-AR) activation can lower plasma glucose in diabeticrats lacking insulin. We investigated the change in A1-AR gene expression in diabeticrats. 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 diabeticrats (STZ-diabeticrats) 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-diabeticrats. 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-diabeticrats to about 250% of that in normal rats. Exogenous insulin at a dose sufficient to normalize the plasma glucose of STZ-diabeticrats reversed the mRNA level of A1-AR in the liver after a four-day treatment. Similar results were also observed in STZ-diabeticrats that received treatment with phlorizin for four days. Moreover, the protein level of A1-AR was higher in the liver of STZ-diabeticrats 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-diabeticrats to near the normal level. Therefore, correction of hyperglycemia in STZ-diabeticrats 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-diabeticrats. Copyright 2003 John Wiley & Sons, Ltd.
Authors: Bunyen Teng; Jonathan D Smith; Michael E Rosenfeld; Peggy Robinet; Mary E Davis; R Ray Morrison; S Jamal Mustafa Journal: Cardiovasc Res Date: 2014-02-12 Impact factor: 10.787
Authors: Robert Faulhaber-Walter; William Jou; Diane Mizel; Lingli Li; Jiandi Zhang; Soo Mi Kim; Yuning Huang; Min Chen; Josephine P Briggs; Oksana Gavrilova; Jurgen B Schnermann Journal: Diabetes Date: 2011-08-10 Impact factor: 9.461