Human Gut Cells Become Insulin Producers in New Approach

Scientists have converted human gut cells into insulin producers by turning off a single gene in an experiment that suggests a new way forward in treating diabetes.

Using a miniature model of the human intestine, only a few millimeters in size and made from stem cells, the scientists deactivated a gene in the cells tied to metabolic regulation called FOXO1. Once disabled, the cells began producing insulin.

The method, described today in the journal Nature Communications, raises the possibility of replacing insulin-making pancreatic beta cells lost in diabetics by using a drug to retrain patients existing cells. While progress has been made in generating beta cells from stem cells, the method hasnt yet produced ones with all the needed functions, said Domenico Accili, the studys lead author. Plus, such cells would require transplantation.

We provided a proof of principle that we can do this in human tissues and are also very excited that there is a single identifiable target to trigger this process, Accili, professor of medicine at Columbia Universitys Naomi Berrie Diabetes Research Center in New York, said in an interview. This is what the pharmaceutical industry is interested in -- make a chemical and do what we did in test tubes to administer to persons with diabetes and teach their gut cells to become beta cells.

The results build on research two years ago by Accili and his team that first tested the approach in mice, successfully converting gut cells into insulin-making cells. That work has since received independent confirmation from another group. In the human cell experiment, gut cells started releasing insulin after seven days and only in response to glucose.

Now that Accili and his team have shown it works in human cells, their next step is to develop a drug to test in people. Accili said its possible that there could be a compound for clinical trials in a year or two.

Diabetes, which results when the body doesnt use insulin properly or doesnt make the hormone, is the seventh-leading cause of death in the U.S. Insulin is a hormone secreted by the pancreas that helps the body control blood sugar.

Destruction of insulin-making beta cells in the pancreas is the central feature of Type 1 and Type 2 diabetes. In Type 1 diabetics, the cells are destroyed by the immune system and dont produce insulin. In Type 2, in which the body doesnt use insulin properly, beta cells become progressively dysfunctional.

One advantage to this experimental approach is that the gastrointestinal tract is partly protected from attack by the immune system, making gut cells less susceptible to destruction, Accili said.

A treatment for diabetes that doesnt require daily insulin injections would change the treatment landscape for the 29 million diabetics in the U.S. However, its likely that any potential drug would first be evaluated for Type 2 diabetes, because of concerns of testing in Type 1 diabetics going without insulin injections, he said.

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Human Gut Cells Become Insulin Producers in New Approach