We have confirmed that the gut production of insulin, a discovery we originally made in mice, can also occur in people with diabetes—Domenico Accili
In 2012, Domenico Accili, MD, the Russell Berrie Foundation Professor of Diabetes, and his colleagues published papers on two different discoveries with important implications for treating and ultimately, for curing diabetes. Subsequent work in Dr. Accili’s laboratory has moved these discoveries closer to translation into patients with diabetes.
The first paradigm-shifting discovery, was that cells in the intestines of mice could be manipulated to produce insulin. In mice, as well as humans, the pancreas is the source of insulin. The intestine (or gut) does secrete other hormones, just not insulin. Dr. Accili was able to induce the gut to secrete insulin, opening up the possibility that gut insulin could substitute for pancreatic insulin as a possible cure for diabetes.
His second major discovery upended the longstanding idea that the end-result of all forms of diabetes was that the insulin-secreting beta cells of the pancreas died off. Dr. Accili showed instead that the beta cells reverted to a less mature state – they de-differentiated instead of dying – opening up the possibility that the beta cells could be re-differentiated and coaxed back to producing insulin.
On April 2, 2014 at the Berrie Center Diabetes Research Panel to be held at the University Club, Dr. Accili, will discuss exciting new findings that will help take both projects from mouse models, to the next step—clinical drug trials for people diabetes. “The news is exciting on both fronts,” said Dr. Accili, who received the 2013 Donald F. Steiner Award for outstanding achievement in diabetes research at the University of Chicago. “We have confirmed that what has occurred in mice can also occur in humans.”
In order to test whether the human gut can be induced to secrete insulin, Dr. Accili and his team collaborated with the Berrie Center stem cell research group who has pioneered creation of patient-specific beta cells from skin cells taken from type 1 diabetes patients at the Berrie Center. Dr. Accili’s group created patient-specific gut-cells from these skin biopsy cells. Just as the gut cells in mice could be modified to produce insulin, the human gut cells created from skin cells can also be induced to produce insulin.
“We now know that the human gut has exactly the same potential to produce insulin as the mouse gut. More importantly, we know that this can be achieved in several ways,” reported Dr. Accili, who is working with two pharmaceutical companies on developing oral drugs that turn on gut insulin secretion that can be tested in patients with diabetes. “We’ve cleared two huge hurdles,” said Dr. Accili “and we are on the way to making the gut a new source of insulin for people with diabetes.”
Dr. Accili is also working with two pharmaceutical companies on his second line of research—that beta cells do not die off in people with diabetes, but instead revert to a more immature, de-differentiated cell type—on new chemical strategies that would reverse the de-differentiation.
“We published this research to much fanfare,” recalled Dr. Accili, “and the question has been, does it happen only in mice or does it happen in people? Now we know that it happens in people, which opens up an entire new field of research into different drugs for diabetes.”
The new drugs, explained Dr. Accili, would represent a new way of treating diabetes. “The oral drugs we have right now push the beta cells to make more insulin,” said Dr. Accil. “They try to get sick cells to work even harder. The new drugs will try to revive the beta cell, to awaken them if you will. This work is important for people with both type 1 and type 2 diabetes.”
In addition to Dr. Accili, the April Diabetes Research Panel scientists are Berrie Center and Columbia faculty members, Robin Goland, MD, J. Merrill Eastman Professor of Medicine and Berrie Center Co-Director and Rudolph Leibel, MD, Christopher Murphy Professor of Pediatrics and Berrie Center Co-Director, who will moderate the panel; Wendy Chung, MD, PhD, Associate Professor of Pediatrics, a renowned clinical and molecular geneticist; Rebecca Haeusler, PhD, an Assistant Professor of Pathology and Cell Biology, who studies the connection between diabetes and cardiovascular diseases; Dieter Egli, PhD, Assistant Professor of Pediatrics, a stem cell scientist whose discovery of a new way to make patient-specific stem cells was named Time Magazine’s #1 medical discovery of 2011; and Michael Rosenbaum, MD, Professor of Pediatrics, an expert on the physiology of body weight regulation.