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Physicians Update

 
Spring 2013

Some Patients May Avoid Future Diabetes

Using Cells Normally Discarded During Surgery

The islet of Langerhans (center), found in the pancreas, secretes the hormones insulin and glucagon, which control blood-sugar levels. The islet of Langerhans (center), found in the pancreas, secretes the hormones insulin and glucagon, which control blood-sugar levels.

Chronic pancreatitis is an inflammatory disease that causes recurrent episodes of pain and increases the risk for developing pancreatic cancer. Gallstones and excess alcohol use are common causes of chronic pancreatitis among adults, while genetic disorders are most often associated with the condition in children. When drugs are no longer effective in managing the symptoms of chronic pancreatitis, partial or total removal of the pancreas (pancreatectomy) may become the last resort to alleviate patients’ debilitating pain.

“Surgery is very effective in eliminating pain and cancer risk in patients with chronic pancreatitis,” explains Howard A. Reber, MD, director of the UCLA Center for Pancreatic Diseases. “The problem is that patients lose the ability to produce insulin with the removal of all or part of their pancreas, and those patients will develop diabetes.”

In some patients, however, diabetes may be avoided by using a procedure called auto-islet transplantation. During the procedure, islets, which are clusters of pancreatic cells that sense blood-sugar levels and release insulin to maintain normal levels, are saved during pancreatectomy, isolated in the laboratory and then infused back into the patient’s body through a catheter inserted into the liver. Islet cells can then continue to produce insulin. Because islets are generated by the patient’s own pancreas, rejection does not occur and immunosuppressive drugs are not required. Surgery to remove all or part of the pancreas is common, but the final step is the key to preventing diabetes.

“We’re preserving islets cells that would normally be discarded and using them to potentially prevent future diabetes,” Dr. Reber says. At UCLA, patients who have undergone partial pancreatectomy followed by auto-islet transplantation have avoided both diabetes and insulin dependence. Those who have undergone total pancreatectomy followed by auto-islet transplantation have developed insulin dependence but avoided severe “brittle” diabetes, or unstable diabetes, characterized by dramatic and recurrent swings in glucose. All UCLA patients who have undergone auto-islet transplantation are now pain-free and living normal lives.

While other programs in Los Angeles and across the U.S. can surgically remove the pancreas, UCLA, in an innovative collaboration with a UC San Francisco lab that facilitates isolation of the islets, is one of only a few centers in the United States with the potential to prevent diabetes by performing auto-islet transplantation. Still, just a handful of auto-islet transplantations have been performed at UCLA to date.

“We have good evidence that auto-islet transplantation can free patients from relentless pain and may prevent future diabetes, but people don’t know about the procedure,” says Gerald Lipshutz, MD, surgical director of the Pancreas Transplant Program at UCLA. In addition to improving the prognosis for patients with chronic pancreatitis, the technique also holds the promise for helping patients with related conditions, according to Dr. Lipshutz.

“In part, we are learning how to perform procedures that will be necessary for stem-cell therapies five or 10 years in the future,” Dr. Lipshutz says. “Theoretically, we could biopsy the skin of diabetic patients, isolate and reprogram fibroblasts into stem cells and deliver them safely to the liver so that auto-generated islet cells can be used to produce insulin to overcome diabetes,” Dr. Lipshutz explains. Fibroblasts are cells commonly found in connective tissue that play an important role in healing wounds. Patients with inherited liver disorders (urea cycle or other metabolic disorders) may also benefit from knowledge gained through auto-islet-transplantation procedures.

“Each time we perform auto-islet transplantations, we learn more about how many cells patients can tolerate, refine our transplantation techniques and improve how we monitor patients for current and future procedures related to preventing diabetes and related conditions,” Dr. Lipshutz says.

For more information go to: pancreas.ucla.edu





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