Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism

Figure 3 Integrated model of Zac1’s role in β-cell function and glucose metabolism. Zac1 DNA-binding at downstream target genes confers transcriptional activation or repression in a partly tissue-specific manner in mice. In this respect Zac1 binding represses Pac1 and Rasgrf1 in pancreatic β-cells leading to an impaired insulin-secretory response and GSIS (left). Additionally, Zac1 upregulation of the transcription factors Pparγ and Tcf4 may translate in enhanced expression of their downstream targets Ucp-2, Pten, and p57^Kip2 with an inhibitory role in GSIS and β-cell proliferation (middle). Moreover, Zac1-dependent transactivation of Socs3 may attenuate growth factor and insulin signaling in β-cells and peripheral tissues, respectively (right).