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New beta cell biomarker discovered in research involving Greiner lab: What does it mean for future diabetes research?

Unique UMass DCOE "humanized mice" used for the in-vivo imaging

New research published in Cell Metabolism has identified a biomarker for insulin-producing beta cells.  The laboratory of UMass Diabetes Center of Excellence (DCOE) co-director Dale Greiner, PhD, Dr. Eileen L. Berman and Stanley I. Berman Foundation Chair in Biomedical Research Professor, collaborated by providing unique immunodeficient mice that allowed for the in-vivo imaging studies. 

Imaging the human beta cells that had been transplanted into these specialized "humanized" mouse models, provides hope for a potential non-invasive way to image human beta cells and monitor the effectiveness of diabetes treatments. 

The paper's senior author, Alvin Powers, MD, director of the Vanderbilt Diabetes Center.  Dr. Powers was the keynote speaker at our UMass Diabetes Day symposium in 2017, shortly after completing his term as President, Medicine and Science of the American Diabetes Association. 

The UMass DCOE is among a few in the world studying human beta cells, the insulin producing cells found only in the pancreas.  Isolating beta cells is very difficult.  UMass DCOE scientists have accomplished it by poking holes in the cells, allowing them to use insulin antibodies to stain and isolate the cells.  However, the beta cells are killed during that process, so they have only studied the dead human beta cells. 

This new data suggests that human beta cells can be positively identified and separated for laboratory studies.  It's the first to report an antibody that binds to the pancreatic beta cell surface, so those cells can be isolated and remain alive for study.  In their studies of the pancreatic islet, the researchers discovered that the NTPDase3 antibody targets only beta cells, not other islet cells. They also found it binds just as well to beta cells from people with diabetes as it does to normal beta cells.  NTPDase3 is not expressed however on beta cells in humans younger than 1 year old, according to the paper. 

This antibody is an important step, but much work remains to be done.  “We ultimately want to develop the capacity to measure the number of insulin-producing beta cells in a living human,” according to David M. Harlan, MD, William & Doris Krupp Professor of Medicine, chief of the Diabetes Division in the Department of Medicine, and co-director at the UMass DCOE.  “That would allow us to measure the number of beta cells in people at risk for diabetes.  We could then attempt to intervene if that number begins to fall.”   

Testing therapies that may increase the number of pancreatic beta cells would be ideal.  Clinical trials to that end are very expensive, because we cannot know how many insulin producing beta cells are in any living person’s pancreas. The UMass DCOE laboratory of Laura Alonso, MD, The George F. and Sybil H. Fuller Term Chair in Diabetes, Associate Professor of Medicine, and director of Beta Cell Biological Studies, is focused on understanding which pathways guide beta cell proliferation. Their goal is to find approaches to make more beta cells, to prevent or treat diabetes. 

“This antibody is an incredibly important tool which has been sought after in the field for many years,” Alonso said.  “An antibody that is able to specifically identify beta cells will allow diabetes researchers to cleanly separate beta cells from all the other cells around them, in order to study them specifically under different conditions.”

While this newly released study provides promise, the challenge of measuring the number of insulin-producing beta cells in the human pancreas, remains a difficult one.  The human pancreas is about the size of a banana, and the beta cells, if lumped together, would be about the size of a pea.  To make matter worse, they are sprinkled throughout the mass of the pancreas, which is located deep within the belly.  That further complicates imaging the beta cells within it.

“If it works in living people, this finding could open the door to beta cell regeneration therapies, because it could allow, for the first time, dynamic measurement of beta cell mass in people over time,” Alonso said of the new antibody.  “If so, this is a major breakthrough.”