The global alliance between Diabetes Research Institute and its partners at Diabetes Research Institute Federation centers has produced a string of research results that have been given cover stories in three of the most prestigious scientific journals in the country – Nature Medicine, Cell Metabolism and Science Translational Medicine – all within a period of about a month. A fourth study is scheduled for release next week in the highly-competitive Proceedings of the National Academy of Sciences (PNAS).
While typically unheard of, even at the finest academic institutions, this peer-reviewed excellence garnered within a short amount of time also demonstrates the strength and productivity of the global collaboration model, which has been the hallmark of the Diabetes Research Institute since its inception.
“The Diabetes Research Institute has become a hub of innovation, where like- minded scientists from all over the world join forces to contribute to ‘outside the box’ research geared to cure diabetes,” explains Camillo Ricordi, M.D., scientific director of the DRI.
The vortex of scientific activity is the result of a multi-year commitment made by the DRI and its Foundation to establish highly integrated international teams to advance cure focused diabetes research. These teams evolved to what is today the DRI Federation, a network of collaborative scientists who have formally agreed to pool knowledge and work together to overcome the traditional barriers of academic competitiveness and geographic distance.
The result of this collaborative network is a blessing for patients with diabetes, as the pace of research has quickened significantly, as demonstrated by these leading publications.
Highlights of each cover story are summarized below:
In Nature Medicine:
DRI researchers discovered that a molecule, acetylcholine, essential for the support of beta cell health and insulin production is, surprisingly, secreted by alpha cells within the islets. It was long believed that this molecule was expressed by nerves but there was no such evidence in this study. Unlike the mouse model, alpha cells in human islets are “coupled”, side-by-side, with the insulin-producing beta cells and rely heavily on co-signaling effects. Beta cell response to glucose was measured and found to improve in the presence of acetylcholine. These discoveries build on previous work by our islet physiology team that showed that alpha and beta cells within human islets are closely associated whereas in mouse islets they are segregated. The implications for diabetes and its prevention are vast, as these findings pave the way for strategies to target alpha cells to improve beta cell health and function. This research was conducted by Drs. Rayner Rodriguez-Diaz and Robin Dando and their colleagues under the supervision of Professor Steven Roper from the Physiology and Biophysics department at University of Miami and, Professors Per-Olof Berggren and Alejandro Caicedo from the DRI.
In Cell Metabolism:
Using in-depth imaging techniques, DRI scientists have been able to observe the unique pattern of nerves (innervation) within a human islet, adding another key element to the understanding of islet cell anatomy. In prior studies, the DRI’s islet physiology team established that the islet architecture varies greatly between species, particularly between human and mouse islets, which has been the widely studied model. The innervation of the islet, long believed to be similar in mice and humans, is found to be drastically different. The mouse islet is much more “hard wired” with nerve fibers penetrating broadly across each islet to reach beta cells and other endocrine cells. In humans, nerve fibers are less prominent and are in contact with blood vessels. Given these differences in islet innervation, it is likely that animals and humans use different mechanisms to achieve nerve control of insulin secretion. As we strive to sustain long term islet health and function, these findings will contribute to developing the optimal environment for islet replacement and stem cell development strategies. This research was conducted by Drs. Rayner Rodriguez-Diaz and Midhat H. Abdulreda and their colleagues under the supervision of Professors Per-Olof Berggren and Alejandro Caicedo.
In Science Translational Medicine:
The use of rituximab, an immunosuppressive drug that was developed for the cure of cancer and of transplant organ rejection, may be utilized to prevent the leakage of protein in the urine that characterizes the early stages of kidney disease. This effect is mediated by a modulation of a specific class of lipids (blood fat) in affected cells, a feature that characterizes also the renal (kidney) complication of diabetes. Novel therapy for the prevention of diabetic nephropathy targeting this class of lipids is now being developed at the DRI under the direction of Dr. Alessia Fornoni in collaboration with Dr. George W. Burke III. Fornoni says the finding is also unique as it uncovers an assay that can be used before kidney transplants to identify patients at risk for recurrent disease and to guide therapeutic decisions, allowing for a personalized medicine approach. The discovery, Fornoni says, “will likely unveil new clinical indications for rituximab beyond its original function and lead to new pathways involved in regulating cell function.”