By Kim Tong-hyung
Staff Reporter
Scientists believe a liver protein, known for triggering inflammatory responses in the organ, could be an unlikely source for a breakthrough in the fight against diabetes.
In a study published by peer-review journal, Cell Metabolism, researchers led by Sungkyunkwan University's Koo Seung-hoi and Chonnam National University's Choi Hueng-sik suggested that improved knowledge about the liver-specific protein CREBH may enable an important step toward a new way of treating the disease.
CREBH, short for cyclic AMP response element-binding protein-H, is a transcription factor that turns on the activity of specific genes in liver cells. Transcription factors refer to the proteins that turn genes on or off or regulate their activity.
Little had been known about the role of CREBH, first identified by researchers at the University of Michigan in 2006, other than that it activates inflammatory response when triggered by stress in the endoplasmic reticulum (ER), which is the part of a cell that makes new proteins.
In their paper, Koo and his colleagues reported that the active expression of CREBH leads to an increase in blood sugar levels, while the suppression of the protein results in the opposite. This is because CREBH induces the generation of glucose in the liver, they said, which contributes to the raised blood sugar levels.
Thus, targeting the transcription factor and disarming could be the key to more effective treatments for diabetes, the researchers said.
"Our research opens the possibility of a development of new types of drugs and therapies based on substances targeting CREBH and the TORC2 protein," said Koo, the first author of the paper.
The suppression of CREBH in diabetic mice led to declined blood glucose levels in the animals, while the over-expression of CREBH led to increased glucose levels. The experiments further showed that CREBH expression was markedly induced by fasting or during the insulin resistance state of the animals.
The researchers also reported that a protein called TORC2, linked with elevated blood sugar in the liver, has a main role in upping the expression of CREBH, which in turn, activates the PEPCK-C and G6Pase genes that were confirmed to be related to glucose production.
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