Effect of hyperglycemic condition on glucose transporter 9 expression in MDCK cell

Abstract

A novel glucose transporter 9 (GLUT9), which is involved in glucose re-absorption processes in kidney, has been shown to be associated with hyperglycemia. However, the regulation mechanisms have not been thoroughly explained. This study aimed to investigate the contributing factors of hyperglycemic condition that could affect GLUT9 expression. The GLUT9 mRNA and protein were measured in semi-quantitative approach by using RT-PCR and Western blot analysis, respectively. The GLUT9 mRNA was significantly decreased by 25 mM glucose and 25 mM sorbitol, which was used to evaluate hyper-osmotic stress effect, whereas, the GLUT9 proteins were noticeably increased by glucose in the MDCK cells treated for 72 hours. Furthermore, extracellular ATP and adenosine, that have been reported to be increased in hyperglycemic condition, significantly increased the GLUT9 protein levels and reached maximum effect at 6 hours period. The GLUT9 protein enhancement effect of adenosine was likely occur through adenosine receptors. Stimulation of protein kinase A could inhibit the effect of adenosine treatment. Our results demonstrated that the decrease of GLUT9 mRNA expression in long-term treatment with glucose at high concentration might relate to hyper-osmotic stress effect. Moreover, the extracellular ATP and adenosine, found to be increased during hyperglycemia, may be the major components that enhance GLUT9 protein expression via purinergic system preferentially through adenosine receptor activation and protein kinase A inhibition.