Added knowledge of the mechanisms causing diabetes

Our superhero, pancreas, needs some help! Osaka University researchers have discovered a
mechanism through which a lack of insulin can be transmitted back to the pancreatic cells that
create insulin, revealing a potential new therapeutic target for diabetes.

Type 2 diabetes affects an estimated 400 million individuals globally, and insulin control in the
body is still remain unclear. Type 2 diabetes develops when the pancreas fails to produce enough
insulin, the hormone that regulates sugar utilization and storage, to meet physiological demands.
If the body's demand for insulin is not met,
the cells in the pancreas that create insulin
can normally multiply to increase their
numbers. It is uncertain, however, what
substances are released by insulin-
receiving tissues or cells to indicate a
shortage of insulin to pancreatic cells.
Researchers discovered that a protein
called T-cadherin may be involved in
providing feedback to insulin-producing
pancreatic cells and modulating their
proliferation in a study published in
iScience. T-cadherin is often found on the
cell surface and is best recognized as the
binding partner for adiponectin, a protein
released particularly by fat-storing cells. T-
cadherin, on the other hand, is secreted in
heretofore unrecognized soluble forms and can function as a humoral factor, or a molecule
conveyed through the circulatory system, according to the researchers. They not only discovered
that T-cadherin responds to insulin deficit, but they also discovered that mice genetically
modified to lack T-cadherin had poor glucose tolerance when fed a high-fat diet.
"RNA sequencing analysis, which was utilized to investigate genome-wide gene expression levels,
indicated lower expression of Notch signaling proteins in cells from mice lacking T-cadherin," lead
scientist Tomonori Okita and corresponding author Shunbun Kita explain. These proteins are
thought to have a role in the Notch signaling system, which promotes -cell proliferation; this
suggests that soluble T-cadherin stimulates pancreatic β-cells to boost insulin production via the
Notch pathway.
"We then used artificially synthesized T-cadherin to treat isolated mouse pancreatic islets, which
are β cells production regions of the pancreas," says senior author Iichiro Shimomura. "This
therapy increased Notch signaling in mouse islets, which could lead to β -cell proliferation." These
findings are exciting because they suggest that T-cadherin could be used in the fundamental
treatment of diabetes.