It is estimated that over 400 million individuals worldwide have type 2 diabetes, although insulin control in the body is still poorly understood.
Type 2 diabetes develops when the pancreas fails to produce enough insulin, the hormone that regulates sugar use and storage, to meet physiological demands.
If the body’s need for insulin is not being satisfied, the insulin-producing cells in the pancreas, sometimes referred to as β cells, can frequently multiply to expand their population.
However, it is uncertain what substances are released by the tissues or cells that receive insulin to alert the pancreatic cells to the absence of insulin.
Now, Osaka University researchers have uncovered a mechanism by which insulin deficiency can be communicated back to the pancreatic cells that make insulin, thereby providing a potential new therapeutic target for diabetes.
According to the findings of a study that was recently published in the journal iScience, researchers discovered that a molecule known as T-cadherin may be involved in controlling the proliferation of insulin-producing pancreatic cells and delivering feedback to those cells.
T-cadherin is a protein found on the surface of most cells; it is best known for being the binding partner for a molecule called adiponectin, a substance released exclusively by cells that accumulate fat.
But the researchers showed that T-cadherin is also secreted in soluble forms that had not been described before and can act as a humoral factor, which is a molecule that moves through the bloodstream.
They not only found that T-cadherin responds to a lack of insulin, but they also showed that mice engineered to lack T-cadherin had a hard time handling glucose when given a high-fat diet.
“RNA sequencing analysis, used for investigating genome-wide gene expression levels,” as explained by the authors of the study, “revealed decreased expression of Notch signaling proteins in the β cells of mice lacking T-cadherin.”
These proteins are involved in the Notch signaling pathway, which is thought to increase the number of β-cells. This suggests that soluble T-cadherin uses the Notch pathway to tell the pancreatic -cells to make more insulin.
“We then used artificially synthesized T-cadherin to treat isolated mouse pancreatic islets, which are parts of the pancreas that contain β cells” adds senior author Iichiro Shimomura. “This treatment promoted Notch signaling in the mouse islets, which could in turn induce β-cell proliferation.”
These results suggest that T-cadherin may one day play a significant role in the treatment of diabetes.
Source: 10.1016/j.isci.2022.105404
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