Soluble T-cadherin is a novel secreted factor that promotes proliferation of pancreatic beta-cells in response to insulin deficiency. CREDIT Shunbun Kita
Wake up pancreas, it’s time for work! Researchers led by Osaka University have now identified a mechanism by which a lack of insulin may be reported back to the pancreatic cells that produce insulin, identifying a potential new therapeutic target for diabetes.
Type 2 diabetes is estimated to affect over 400 million people worldwide, and yet insulin regulation in the body is still not fully understood. Type 2 diabetes occurs when the pancreas cannot supply sufficient insulin, the hormone that controls sugar use and storage, to meet physiological demands. The cells in the pancreas that make insulin, known as β cells, can usually proliferate to increase their numbers if the body’s insulin demand is not met. However, what factors are released from the insulin-receiving tissues or cells to signal the lack of insulin to the pancreatic β cells is unknown.
In a study published in iScience, researchers found that a molecule called T-cadherin may provide feedback to the insulin-producing pancreatic cells and control their proliferation. T-cadherin is usually present on the cell surface and is best known as the binding partner for adiponectin molecule—a factor secreted specifically by cells that store fat. However, the researchers showed that T-cadherin is also secreted in previously undescribed soluble forms and can act as a humoral factor, i.e., a molecule transported through the circulatory system. They recognized that T-cadherin responds to insulin deficiency and demonstrated that mice genetically engineered to lack T-cadherin had an impaired glucose tolerance when fed with a high-fat diet.
“RNA sequencing analysis, used for investigating genome-wide gene expression levels, revealed decreased expression of Notch signalling proteins in the β cells of mice lacking T-cadherin,” explained lead author Tomonori Okita and corresponding author Shunbun Kita. These proteins play a role in the Notch signalling pathway that promotes β-cell proliferation; this suggests that soluble T-cadherin signals the pancreatic β-cells to increase insulin production via the Notch pathway.
“We then used artificially synthesized T-cadherin to treat isolated mouse pancreatic islets, which are parts of the pancreas that contain β cells” explains senior author Iichiro Shimomura. “This treatment promoted Notch signaling in the mouse islets, which could induce β-cell proliferation.” These findings indicate that T-cadherin could be applied in the fundamental treatment of diabetes.