| GLUT4 is the insulin-responsive facilitative glucose transporter expressed in adipose and muscle tissues. In diabetes mellitus total GLUT4 protein is significantly reduced due to a decrease in GLUT4 gene transcription. Elevation of total GLUT4 protein can translate into a considerable increase in the maintenance of glucose homeostasis. Therefore, our lab is investigating two regulatory elements of GLUT4 expression: the MEF2 transcription factor family and a novel transcription factor named the GLUT4 Enhancer Factor (GEF). As no previously utilized in vitro cell system fully recapitulates correct GLUT4 regulation, we examined the dispersed adipocyte cell model in its regulation of the GLUT4 promoter. We identified a hyperphosphorylation of MEF2A that correlated with decreased GLUT4 promoter activity in dispersed adipocytes. As little is currently known about the functioning of GEF, we have also further characterized how this protein regulates the GLUT4 promoter. We have examined how GEF homo- and hetero-oligomerizes with transcriptional regulators, including the MEF2 family and HDAC5. Furthermore, we have identified a novel function for MEF2A, namely causing an increase in DNA binding affinity of GET for the GLUT4 promoter. We have studied how upstream signaling cascades and splice variation might regulate the GLUT4 promoter via GEF and MEF2A and MEF2D. We now hypothesize that GEF and MEF2A/2D can form a platform on which signaling cascades and transcriptional coregulators can govern GLUT4 promoter activity. |
