CREB1 and Insulin resistance: In the meantime, Luan B et al. reported that targeted disruption of CREB or cAMP-regulated transcriptional coactivators 2 and 3 (CRTC2/3) in macrophages downregulated M2 marker gene expression and promoted insulin resistance and facilitated insulin resistance, demonstrating that CREB-related molecules could initiate the human innate immune system [37].