Importantly, treatment with the pharmacologic ERs agonists caused significant increases in the membrane ERα and ERβ expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of type 2 diabetes mellitus mice.
Previously, we demonstrate that FXR inhibits GLP-1 secretion via interacting with CREB to inhibit the transcriptional activity of CREB, thus promoting the development of type II diabetes.
In this study, we aimed to explore genetic variations in CREB1 promoter region and determine whether these loci affect transcriptional activity and risk on type 2 diabetes (T2D).
Our findings suggest that the failure of the negative feedback regulation of CREB is the primary cause for β-cell dysfunctions under conditions of pathogenic hyperglycemia, and PP2A can be a novel target for future therapies aiming to protect β-cells mass in the late transitional phase of non-insulin dependent type 2 diabetes (NIDDM).