The effect of glucose, adenosine-5’-triphosphate, and adenosine on glucose transporter 9 expression in MDCK cells

jamras kanchanapiboon, Thitima Pengsuparp

Abstract


This study aimed to investigate the effect of glucose, adenosine triphosphate (ATP) and adenosine and their concentration dependence on GLUT9 expression in hyperglycemic conditions. These compounds have been reported to be associated with hyperglycemia in both animal and human. Extracellular ATP and adenosine exert their activities to regulate the pathophysiology through purinergic signaling. Their involvement was evaluated using non-selective antagonists such as caffeine (for P1 receptor) and suramin (for P2 receptor). Purinergic P1 receptors are associated with adenylate cyclase leading to increase or decrease the content of intracellular cAMP that plays a role in protein kinase A activation. The GLUT9 mRNA and protein levels were measured by reverse transcription-polymerase chain reaction and Western blotting analysis, respectively. The GLUT9 protein levels were increased significantly when the cells were treated with 25 mM and 50 mM glucose, in a concentration-dependent manner. The protein levels were also increased when cells were treated with 100 µM ATP and 100 µM adenosine for 6 h, whereas only adenosine decreased GLUT9 mRNA levels. Further study of adenosine-induced GLUT9 expression revealed that the observed effect was inhibited by caffeine. Moreover, stimulation and inhibition of protein kinase A could decrease and increase the GLUT9 protein levels, respectively. Therefore, glucose could increase GLUT9 protein levels, and extracellular ATP and adenosine might be major contributing factors in enhancing the GLUT9 protein expression via purinergic system preferentially through P1 receptor activation and protein kinase A inhibition.

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References


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