A promising treatment option is transplanting pancreatic islet cells, but that therapy has presented clinicians with clear challenges. Currently, insulin independence can only be achieved for a limited time and often requires a second procedure. The limited success is due to insufficient islet cells and their progressive failure over time. That has left physicians with an urgent need to improve methods to expand the number of islet cells by making them proliferate faster and die slower. Now, Miller School researchers have played a major role in a discovery that could benefit millions of diabetes patients.
An international team of researchers led by the University of Miami Miller School of Medicine and the University of Dresden has discovered a potential method to improve those results using growth hormone-releasing hormone (GHRH). Andrew V. Schally, Ph.D., M.D.h.c., D.Sc.h.c., the 1977 Nobel Prize winner for Physiology or Medicine, Distinguished Medical Research Scientist of the Department of Veterans Affairs, and Distinguished Professor of Pathology, and Norman Block, M.D., professor of pathology, urology, oncology and biomedical engineering and the L. Austen Weeks Family Professor of Urologic Research, in concert with Stefan Bornstein, M.D., and Barbara Ludwig, M.D., of the Carl Gustav Carus University Hospital in Dresden, Germany, and their colleagues led an international team of scientists who have published their findings in the June 28 online issue of the Proceedings of the National Academy of Sciences.
Previously, several growth factors that may have the potential for enhancing beta cell mass have been identified. However, there has not been much focus on the potential role of GHRH or its agonists. Growth hormone-releasing hormone stimulates the release of growth hormone from the pituitary gland and has been a primary focus of research for Schally. Recently, Schally and another Miller School team of researchers demonstrated that an agonist of GHRH has a favorable effect on the heart, reducing infarct size.
Schally, Block and the Dresden scientists showed that a synthetic agonist of GHRH, JI-36, caused a significant increase in islet cell proliferation and a reduction in cell death or apoptosis. Islets are made up of several types of cells including beta cells, which are the cells responsible for producing insulin. The researchers found that a synthetic antagonist of GHRH reversed the results, indicating that the GHRH mechanism was the operating factor in this change. This particular agonist reduced the programmed cell death and pre-treatment improved the metabolic function and engraftment of the cells following transplantation. In fact, islets treated with the GHRH agonist before transplantation into diabetic mice were able to produce normal glucose levels in the blood earlier and more consistently than islets without JI-36.
The GHRH agonist, JI-36, in vivo was able to increase cell size leading to increased insulin production and quicker insulin production in response to a glycemic stimulus. Block says this “tells us GHRH agonists will be a new and unique pharmacologic therapy for promoting islet cell graft growth and proliferation in diabetic patients.”
“Our hope,” says Schally, “is that with this discovery, we’ve provided a novel treatment which will improve the management of this disease for millions of patients.”