iScience: New insights into the pathogenesis of diabetes

Wake up, pancreas, it's time to work! Researchers led by Osaka University have now identified a mechanism by which insulin deficiency may feed back to insulin-producing pancreatic cells, finding a potential new therapeutic target for diabetes
.

Type 2 diabetes is estimated to affect more than 400 million people worldwide, but the regulation of insulin in the body is still not fully understood
.
Type 2 diabetes
occurs when the pancreas is unable to provide enough insulin (the hormone that controls sugar use and storage) to meet physiological needs.
If the body's need for insulin is not met, the insulin-producing β cells in the pancreas usually proliferate to increase their number
.
However, it is unclear what factors signal pancreatic β cellular insulin deficiency
from insulin-receiving tissues or cells.

The researchers, published in iScience, found that a molecule called T-cadherin may be involved in providing feedback to insulin-producing pancreatic cells and controlling their proliferation
.
T-cadherin is normally found on the cell surface and is best known as a binding partner to the adiponectin molecule, a factor
specifically secreted by cells that store fat.
However, the researchers showed that T-cadherin is also secreted in a previously described soluble form and can act as a humoral factor, a molecule
transported through the circulatory system.
Not only did they recognize that T-cadherin responds to insulin deficiency, but they also demonstrated that T-cadherin-deficient mice were genetically engineered to impaired
glucose tolerance when fed high-fat foods.

Lead author Tomonori Okita and corresponding author Shunbun Kita explain: "RNA sequencing analysis to investigate genome-wide gene expression levels showed a decrease
in the expression of the Notch signaling protein in β cells of mice lacking T-cadherin.
" These proteins play a role in the Notch signaling pathway, which is thought to promote β cell proliferation; This suggests that soluble t-cadherin signals pancreatic β cells via the Notch pathway to increase insulin production
.

Senior author Iichiro Shimomura explains: "We then used synthetic T-cadherin to treat isolated mouse islets, which are the parts of
the pancreas that contain β cells.
" "This treatment promotes Notch signaling in mouse islets, which in turn may induce β cell proliferation
.
" Encouragingly, these findings suggest that T-cadherin can be used in the basic treatment of
diabetes.