4/6/2013
Scientific Profile: Domenico Accili, MD

Russell Berrie Foundation Professor of Diabetes

Director, Columbia University Diabetes & Endocrinology Research Center

 

So much of scientific discovery happens through serendipitous findings. This is a story about two such discoveries that have huge potential implications for the future of people with type 1 diabetes and type 2 diabetes.

Insulin-Produing Gut Cells 

He wasn’t trying to get the gut to produce insulin. But that is, in fact, what happened when Domenico Accili, MD, and his research team at Columbia University’s Naomi Berrie Diabetes Center “knocked out” the transcription factor on the insulin gene in mice.

Transcription factors are small chemicals that tell the DNA in cells what to do - think of them as operating instructions, in this case for the hormone insulin. When the transcription factor known as ‘foxo1’ was knocked out entirely, insulin started to be produced, but not in the pancreas – it happened in the gut.

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The findings made international news when they were first published in the scientific journal Nature Genetics in March 2012. Since that time, the Berrie Center, together with laboratories and pharmaceutical companies around the world, have begun to contemplate and act upon the significance of the discovery.

If scientists can replicate the experiment in human beings, they could potentially create a new source of insulin - in the gut instead of the pancreas - for people with type 1 diabetes.

The Accili laboratory is hard at work trying to prove that what occurs in mice will also occur in people with type 1 diabetes. “We are currently testing this discovery in a human cell culture system of the gut that we have developed from skin cells taken from patients at the Berrie Center with type 1 diabetes,” reports Dr. Accili. “This is the necessary next step – and our progress to date has been very promising.” Significant additional funding is needed to move this project forward, toward clinical trials.

Re-Awakening Beta Cells

An equally important discovery for people with type 2 diabetes was also made last year in Dr. Accili’s lab. His research team showed that the pancreatic insulin-producing cells in mice with type 2 diabetes did not die off with the progression of the disease - as scientists previously thought. Instead, they revert back to an earlier stage of development.

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“These beta cells aren’t dead at all,” said Dr. Accili, “They actually become what we call progenitor cells, or cells that have not yet taken on all the features of insulin producing cells. Once we can prove that a similar process goes on in patients with type 2 diabetes, we think we know of ways in which this de-differentiation can be reversed and the cells can be tweaked back into insulin-producing cells.”

Dr. Accili will share more about his exciting discoveries at the Diabetes Research Panel on April 29 at the University Club in New York City. He will be one of five Columbia University scientists on hand to talk about the future of diabetes treatments and cures.

Click here to support Dr. Accili's research at the Naomi Berrie Diabetes Center.