Release date: 2015-02-28
Recently, researchers from the United States published their latest research results in the international journal cell reports. They found that the CREB signaling pathway can promote insulin secretion by inducing the expression of the transcription factor MafA. In the process of chronic hyperglycemia, the expression of PKIB is up-regulated, inhibiting the CREB activity of β-cells, thereby affecting the expression of MafA, leading to β-cell damage. .
The researchers point out that a sustained increase in blood glucose leads to a compensatory increase in islets, which in turn leads to degeneration of beta cell function, which ultimately leads to diabetes. Previous studies have found that cAMP can regulate incretin secretion by inducing PKA activation. Blocking the cAMP pathway in beta cells leads to severe glucose intolerance and beta cell apoptosis, while enhancing PKA activity promotes insulin secretion. cAMP promotes the expression of related genes through PKA-mediated phosphorylation of CREB family activators and dephosphorylation of CRTC.
The researchers found that knocking out the CREB coactivator CRTC2 in beta cells caused a drop in insulin levels in the circulatory system, leading to oral glucose tolerance in mice. It was confirmed by experiments that CRTC2 can promote β cell function by stimulating the transcription factor MafA expression. In chronic hyperglycemia, activation of HIF1-dependent PKIB disrupts the cAMP signaling pathway in islet cells, resulting in altered gene expression and disordered glucose metabolism. At the same time, inhibition of PKIB gene expression enhances islet function in obese background.
Taken together, this study found that up-regulation of PIKB in chronic hyperglycemia inhibits PKA activity, affecting the CREB signaling pathway, and found that the transcription factor MafA can be regulated by CREB, affecting the synthesis and secretion of insulin by β cells. These results illustrate how the interaction between nutrient and hormonal pathways promotes islet cell function damage.
Source: Bio Valley
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