Not in the pancreas alone: ​​a surprising discovery opens up new possibilities for treating diabetes

The exclusive “franchise” for the production of insulin in the human body is reserved for beta cells in the pancreas – so at least it is commonly thought. In a study published today (Thursday) in the scientific journal Nature Medicine, scientists from the Weizmann Institute of Science and the Yale University in the United States discovered cells that produce the hormone essential for regulating blood sugar levels in an unexpected place: the fetal gut. The discovery opens new directions for the development of treatments for diabetes that affect hundreds of millions of patients worldwide.

In the developing fetus there are many cells that have not yet decided what to do when they grow up. This is especially true for intestinal cells: Although this digestive organ develops in the second trimester of pregnancy, as long as the fetus is fed through the umbilical cord, the fetal intestine is disabled from its traditional functions, and its cells can engage in unusual tasks (while waiting for food to arrive).

To detect these unconventional activities in the fetal gut, Prof. Shalev Itzkowitz of the Department of Molecular Biology of the cell at the Institute of Prof. Lisa Konikova of the Yale School of Medicine. A joint research team led by the two groups, led by Adi Egozi, a doctoral student in Prof. Itzkowitz’s group, first mapped the gene expression profile in the intestinal cells of embryos using advanced technology to floor the genetic material at the single cell level in thousands of cells simultaneously. The gene expression map obtained from 36,000 intestinal cells in the fetus was compared by researchers to a parallel map in newborns.

The comparative study made a surprising discovery: cells outside the pancreas expressed in some embryos the gene for insulin production. These were K / L cells – cells that secrete hormones in the small intestine. These cells in the fetal small intestine, henceforth called FIKL, expressed not only the gene that produces insulin but a complete molecular program designed to support the activity of this hormone, including genes that function as sugar sensors or those responsible for secreting the hormone from the cell.

The surprising discovery for the treatment of diabetes (Photo: Weizmann Institute)

In addition, similar to beta cells, FIKL cells produced insulin in particularly large quantities and it was found that the organization of the molecules in the two cell types was similar: messenger RNA molecules, which hold the recipe for insulin production, were closer to the cell inside. Ready and cashed.

“The similarity between beta cells and FIKL cells is not entirely surprising, since the pancreas and small intestine are formed from the same fetal tissue around the fifth week of pregnancy,” says Prof. Itzkowitz. However, it is not yet clear what the role of insulin-producing cells is in the fetal gut. It is possible that the genetic program for hormone production was activated in fetal cells in response to maternal diabetes or that insulin production was intended for “local” purposes: to support the rapid development of the gut. It should be noted in this context that the cells tested in the study were taken from a fetal tissue bank – and the researchers have no information about the health status of the mothers and their sugar levels during pregnancy.

“It is not clear how intestinal insulin production stops after birth, but it is possible that this dormant program can be awakened in diabetics,” says Prof. Itzkowitz. “If this is possible, intestinal mucosal cells may be a wonderful source of insulin production, as they are constantly regenerating.”

In diabetes, beta cells in the pancreas are destroyed by the immune system (“juvenile diabetes” or type 1 diabetes) or alternatively collapse under the load of sugar in the body (type 2 diabetes). Researchers trying to cure diabetes through cell transplants have so far used mostly stem cells or engineered cells that caused them to produce insulin. “The advantage of the cells we discovered in embryos is that they naturally contain the action plan for producing insulin,” says Prof. Konikova. “If we can identify the molecular signals that turn this program on or off, we may one day be able to activate it when needed.”

The study involved Dana Lebichucha-Loha and Blake McCourt of Yale School of Medicine; Dr. Keren Behar Halpern and Dr. Lydia Farrak of the Institute’s Cell Biology Department; And Xiaojing Ann, Fujing Wong and Dr. Kung Chen of the University of Pittsburgh.

By Editor

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