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Researchers Confirm Entire Islet "Organ" is the Master Regulator of Blood Glucose Levels

Findings have significant implications for cell-based therapies to cure type 1 diabetes

MIAMI, FL – March 7, 2018 – Scientists from the Diabetes Research Institute, the University of Miami, and the Karolinska Institutet in Sweden have confirmed that pancreatic islets have the overall responsibility for maintaining normal blood glucose levels in the body. Moreover, the cell-to-cell interactions within the islet itself are critical to the body’s ability to fine-tune its distinctive glucose level. The startling findings, published in Cell Metabolism, have significant implications for islet transplantation and regenerative cell therapies, suggesting that the ability to restore normal blood sugar levels in people with type 1 diabetes may require more than replacing only the beta cells.

“In the 1980s, we and others had reported that the donor species determines the glycemic set point and glucose levels in recipients of pancreatic islet transplants. However, the mechanism was unknown. This study sheds some light on the mechanism responsible for this effect, indicating that glucagon-secreting alpha cells are necessary to fine-tune the human ‘glucostat,’ with important implications that could affect the development of novel therapeutic strategies in type 1 diabetes,” said Camillo Ricordi, M.D., director of the Diabetes Research Institute and the Stacy Joy Goodman Professor of Surgery at UM.

The Islets of Langerhans, commonly referred to as islets, are actually cell clusters that function like an organ unto itself. Each islet contains approximately 3,000 to 4,000 cells, including insulin-producing beta cells and glucagon-secreting alpha cells, all of which work together to regulate blood sugar levels.

The Master Regulator
In this study, the researchers transplanted pancreatic islets from donor organs and from different species into diabetic and non-diabetic mice. They then measured blood glucose levels and glucose tolerance in the recipient mice.

“We found that the engrafted islets transferred the glycemic levels of the donor species. This indicates that the pancreatic islets have the overall responsibility for maintaining normal blood glucose levels,” says principal investigator Per-Olof Berggren, Ph.D., head of Cell Biology and Signal Transduction at the Diabetes Research Institute and professor at the Rolf Luft Research Centre for Diabetes and Endocrinology at Karolinska Institutet in Sweden.

The researchers also discovered that in humans, in contrast to rodents, the cells releasing the hormone glucagon in the pancreatic islets are of crucial importance for the regulation of insulin-producing cells, and thus the regulation of blood glucose levels.

“Our previous work showed us that the arrangement of the endocrine cells within the pancreatic islet had huge influence on the islet function; the current study now adds to that body of knowledge and shows that the complex communication between the different islet cells determines the set point of blood sugar levels,” said Midhat Abdulreda, Ph.D., Assistant Professor of Surgery at the Diabetes Research Institute.

Implications for cell replacement approaches
The results of the study also demonstrate the importance of using human pancreatic islets for cell-based therapies in people with type 1 diabetes. According to the researchers, in order to develop a biological cure for diabetes using stem cell technology, it will be necessary to obtain all the cells found in the pancreatic islets or create artificial islets complete with all the cell components prior to transplantation into patients.

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About the Diabetes Research Institute
The Diabetes Research Institute at the University of Miami Miller School of Medicine leads the world in cure-focused research. As the largest and most comprehensive research center dedicated to curing diabetes, the DRI is aggressively working to develop a biological cure by restoring natural insulin production and normalizing blood sugar levels without imposing other risks. Researchers have already shown that transplanted islet cells allow patients to live without the need for insulin therapy. Some study participants have maintained insulin independence for more than 10 years. The DRI is now building upon these promising outcomes by developing a DRI BioHub, a bioengineered “mini organ” that mimics the native pancreas. While various BioHub platforms are being tested in preclinical and clinical studies, the DRI is also developing strategies to eliminate the need for anti-rejection drugs, reset the immune system to block autoimmunity, and develop and unlimited supply of insulin-producing cells. For more information, please visit DiabetesResearch.org, call 800-321-3437, or Tweet @Diabetes_DRI.

 

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