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In Vivo
DIABETES INNOVATION


Using a PET imaging technique commonly used to study the brain, diabetes researchers in
Paul Harris
Paul Harris
the Naomi Berrie Diabetes Center have captured pictures of insulin-producing cells inside a living animal.
   The new PET technique, which measures total beta cell mass, was developed by Department of Medicine researchers Paul Harris, Ph.D., the principal investigator, and Antonella Maffei, Ph.D., associate research scientist, and other CUMC researchers.
If the long-awaited technique also works in humans, PET imaging will give researchers and clinicians a way to answer one of the simplest but most pressing questions about diabetes: What happens to the number, or mass, of insulin-producing “beta” cells as the disease progresses?
   “In a sense, people trying to learn about diabetes are completely in the dark about the locus of the disease: insulin-producing beta cells,” says Maren Laughlin, Ph.D., a senior advisor for integrative metabolism at The National Institute of Diabetes & Digestive & Kidney Diseases responsible for funding diabetes imaging projects.
   Although the causes of type I and type II diabetes are complex, diabetes is essentially a disease of the insulin-producing beta cells. In type I, the immune system attacks and kills most of the beta cells in the pancreas, resulting in an inability to produce insulin. In type II, the pancreas produces insulin but the body’s cells are resistant to it, ratcheting up the need for greater amounts. Individuals become diabetic when beta cells no longer meet the increased demand for insulin.
   For both types of diabetes, scientists are now focused on preserving or increasing beta cell mass as they search for new treatments, but without beta
cell imaging, the efficacy of treatments can be difficult to evaluate.
   “We really have a hard time right now figuring out how effective treatments are at preventing the death of beta cells or encouraging new cells to grow,” says Rudolph Leibel, M.D., co-director of the Naomi Berrie Diabetes Center, who is also involved with the new imaging study. Researchers can get an idea of beta cell mass by measuring the level of insulin (or c-peptide, a fragment cut from the precursor for insulin) in blood, but the techniques are too insensitive to give a precise measure. The pancreas also cannot be biopsied because it is a delicate organ located deep in the abdomen. “We need to measure the number of beta cells directly by acquiring images that permit such quantitation,” Dr. Leibel says.
   
Antonella Maffei
Antonella Maffei
For PET imaging to work, the researchers had to find something that distinguished beta cells from other cells in the pancreas and nearby organs. They discovered that beta cells, unlike other cells in the area, produce a molecule called VMAT2.
   Coincidentally, VMAT2 is already used in PET imaging to visualize the brain. Dr. Harris and his colleagues adapted the brain imaging protocol to visualize beta cells, which are dispersed throughout the pancreas, to measure their total mass.
   “It’s really an important finding,” Dr. Laughlin says. “Paul Harris received one of the very first grants we distributed for beta cell imaging and we’re very proud of his work.”
   Dr. Harris and his colleagues have so far only tested beta cell imaging in animals. The next step – seeing if the technique works in people – will soon get under way with patients from the Naomi Berrie Diabetes Center and other volunteers. Dr. Harris is leading these studies, along with Robin Goland, M.D., co-director of the Naomi Berrie Diabetes Center; Ronald Van Heertum, M.D. professor of radiology, and Dr. Leibel.
   “All my patients are very excited and eager to be in our studies,” Dr. Goland says. “If the imaging works in people, it will let us look at the natural history of diabetes in a way that’s never been done before.”
   Diabetes researchers still have basic questions about beta cells such as: How many beta
The ability to visualize insulin-producing beta cells
The ability to visualize insulin-producing beta cells in the pancreas should help answer the most pressing question in diabetes: What happens to the cells during the course of the disease? Image above shows living beta cells in a rat.
cells are present in a healthy pancreas? What happens to them as the disease progresses? and, How many are needed to stave off diabetes?
   “We know that you don’t need a full complement of beta cells to live without diabetes, but we don’t how many cells are sufficient,” Dr. Leibel says. “Hopefully these questions will be answered with this type of technology.”
   Beta cell imaging could also be used in the clinic to guide and evaluate therapies for people with diabetes and to monitor those who have a high risk of developing the disease.
   “High risk individuals are sometimes identified by measuring antibodies to beta cells, but it’s impossible to know if they will get diabetes in six months or in 10 years,” Dr. Harris says. “Taking a picture every year would give a more accurate prediction and let the person know if they are getting better or worse.”
   “This imaging technique is potentially a very important development,” Dr. Leibel says. “I haven’t seen any other technique that’s been so applicable to humans. It has the potential to revolutionize the way we follow patients and develop and evaluate interventions.”
   The research is also supported by a grant from the Columbia Diabetes and Endocrinology Research Center.

—Susan Conova

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