INS and Hyperglycemia: In humans, CRTC2 polymorphisms are associated with an increased risk for T2D44,45, and when CRTC2 levels were manipulated in mice, the corresponding changes in blood-glucose measurements were consistent with our observations in Sam68-deficient mice: modest elevations of CRTC2 increased blood glucose levels and decreased insulin sensitivity15,37, global or liver-specific CRTC2 deletions reduced blood glucose and increased insulin sensitivity15,39,46, and both oligo- and siRNA-mediated CRTC2 inactivation mitigated hyperglycemia in diabetic mice47,48.