A New Approach to Treating Type I Diabetes? Columbia Scientists Transform Gut Cells into Insulin Factories
A study by Columbia researchers suggests that cells in the patient’s intestine could be coaxed into making insulin, circumventing the need for a stem cell transplant. Until now, stem cell transplants have been seen by many researchers as the ideal way to replace cells lost in type I diabetes and to free patients from insulin injections.
The research - conducted in mice - 7was published 11 March 2012 in the journal Nature Genetics.
Type I diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. The pancreas cannot replace these cells, so once they are lost, people with type I diabetes must inject themselves with insulin to control their blood glucose. Blood glucose that is too high or too low can be life threatening, and patients must monitor their glucose several times a day.
A longstanding goal of type I diabetes research is to replace lost cells with new cells that release insulin into the bloodstream as needed. Though researchers can make insulin-producing cells in the laboratory from embryonic stem cells, such cells are not yet appropriate for transplant because they do not release insulin appropriately in response to glucose levels. If these cells were introduced into a patient, insulin would be secreted when not needed, potentially causing fatal hypoglycemia.
The study, conducted by Chutima Talchai, PhD, and Domenico Accili, MD, professor of medicine at Columbia University Medical Center, shows that certain progenitor cells in the intestine of mice have the surprising ability to make insulin-producing cells. Dr. Talchai is a postdoctoral fellow in Dr. Accili’s lab.
The gastrointestinal progenitor cells are normally responsible for producing a wide range of cells, including cells that produce serotonin, gastric inhibitory peptide, and other hormones secreted into the GI tract and bloodstream.
Type 1 diabetes is usually diagnosed in children and young adults, and was previously known as juvenile diabetes. In type 1 diabetes, the body does not produce insulin.
Insulin is a hormone that is needed to convert sugar, starches and other food into energy needed for daily life. Only 5% of people with diabetes have this form of the disease. With the help of insulin therapy and other treatments, even young children with type 1 diabetes can learn to manage their condition and live long, healthy, happy lives.
Drs. Talchai and Accili found that when they turned off a gene known to play a role in cell fate decisions- Foxo1- the progenitor cells also generated insulin-producing cells. More cells were generated when Foxo1 was turned off early in development, but insulin-producing cells were also generated when the gene was turned off after the mice had reached adulthood.
Type 1 Diabetes Statistics
As many as three million Americans may have type 1 diabetes. 1
Each year, more than 15,000 children and 15,000 adults - approximately 80 people per day - are diagnosed with type 1 diabetes in the U.S.2
85 percent of people living with type 1 diabetes are adults.3
The rate of type 1 diabetes incidence among children under the age of 14 is estimated to increase by 3% annually worldwide.
DM is a disproportionately expensive disease; in 2002, the per-capita cost of health care was $13,243 for people with diabetes, while it was $2560 for those without diabetes. The emergency department (ED) utilization rate by people with diabetes is twice that of the unaffected population. Overall, the annual financial cost from diabetes exceeds $100 billion, almost $1 of every $7 dollars of US health expenditures in terms of medical care and loss of productivity.
“Our results show that it could be possible to regrow insulin-producing cells in the GI tracts of our pediatric and adult patients,” Dr. Accili says.
“Nobody would have predicted this result,” Dr. Accili adds. “Many things could have happened after we knocked out Foxo1. In the pancreas, when we knock out Foxo1, nothing happens. So why does something happen in the gut? Why don’t we get a cell that produces some other hormone? We don’t yet know.”
Insulin-producing cells in the gut would be hazardous if they did not release insulin in response to blood glucose levels. But the researchers say that the new intestinal cells have glucose-sensing receptors and do exactly that.