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The ability of adenosine to decrease the concentration of fructose 2,6-bisphosphate in isolated hepatocytes. A cyclic
The Biochemical Journal
|February 15, 1984
Summary
Adenosine and 2-chloroadenosine decrease fructose 2,6-bisphosphate levels in hepatocytes by activating adenylate cyclase. This impacts key enzymes, influencing glucose metabolism and gluconeogenesis.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Regulation
Background:
- Fructose 2,6-bisphosphate is a key regulator of glycolysis and gluconeogenesis.
- Adenosine receptors and their role in cellular signaling are not fully elucidated.
- Understanding the regulation of glucose metabolism is crucial for metabolic disease research.
Purpose of the Study:
- To investigate the effect of adenosine and 2-chloroadenosine on fructose 2,6-bisphosphate levels in isolated hepatocytes.
- To elucidate the signaling pathways involved in adenosine-mediated regulation of glucose metabolism.
- To compare the effects of adenosine and 2-chloroadenosine on gluconeogenesis.
Main Methods:
- Isolated rat hepatocytes were incubated with varying concentrations of adenosine or 2-chloroadenosine.
- Measurements included fructose 2,6-bisphosphate, cyclic AMP, enzyme activities (phosphorylase, pyruvate kinase, 6-phosphofructo-2-kinase, fructose 2,6-bisphosphatase), and gluconeogenesis rates.
- Adenosine transport inhibition and liver supernatant experiments were used to determine the mechanism.
Main Results:
- Adenosine and 2-chloroadenosine significantly decreased hepatocyte fructose 2,6-bisphosphate concentrations.
- These decreases were associated with increased cyclic AMP, activation of phosphorylase and fructose 2,6-bisphosphatase, and inactivation of pyruvate kinase and 6-phosphofructo-2-kinase.
- The effect was mediated by membrane receptors and adenylate cyclase stimulation, independent of adenosine transport, and 2-chloroadenosine stimulated, while adenosine inhibited, gluconeogenesis.
Conclusions:
- Adenosine and 2-chloroadenosine exert their effects on fructose 2,6-bisphosphate via stimulation of adenylate cyclase and membrane receptors.
- These nucleosides modulate key enzymes involved in glucose metabolism.
- Adenosine and 2-chloroadenosine have opposing effects on gluconeogenesis, highlighting differential receptor signaling.