Abstract
Sodium butyrate is widely used to differentiate insulinoma cell lines. However, sodium has been shown to decrease glucose phosphorylation in the liver and heart and decrease the expression of glucose transporter. Since these mechanisms are essential for glucose-induced insulin secretion, the ultimate function of the pancreatic beta-cell, we investigated the effect of sodium butyrate on both glucose-phosphorylating enzymes as well as glucose transport in the pancreatic cell line RIN-m5F. Treatment of RIN-m5F cells with 2.5 mM sodium butyrate for 72 h increased by twofold both hexokinase and glucokinase (GK) activities, as well as the gene expression of GK. Sodium butyrate treatment had no effect on GLUT-1 mRNA levels but increased the GLUT-2 mRNA 3.7-fold. Kinetic analysis of 2-deoxyglucose transport displayed a single curve with Km = 1.2 mM and Vmax = 10.9 pmol/micrograms protein/min in the untreated cells, values similar to the low Km glucose transport reported in the pancreatic beta-cells. This low Km transport component markedly decreased with sodium butyrate treatment, and interestingly a second component with a higher Km appeared, consistent with the increase in GLUT-2 mRNA. We conclude that the differentiating action of sodium butyrate involves increases in GK and GLUT-2 gene expression, which characterizes the differentiated state of the pancreatic beta-cell. However, the inhibitory effect of sodium butyrate on low Km glucose transport needs to be considered in the use of this compound to promote differentiation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.