7 July DRC Director's Report - July 2020 July 7, 2020 By The Fraternal Order of Eagles Diabetes Research Center Eagles, drc, diabetes, iowa, dr. abel, report 0 The greatest risks to long-term health in people with diabetes arise from diabetic complications, particularly cardiovascular disease. However, the mechanisms by which the metabolic changes associated with type 2 diabetes like insulin resistance increases the risk of heart failure are less understood. In a recent publication in JCI Insight, E. Dale Abel, MD, PhD, and other members of the Fraternal Order of Eagles Diabetes Research Center in collaboration with other institutions, have uncovered an important molecular link between diabetes and heart failure. In previous studies, Abel and his fellow researchers revealed that exposure of the heart to higher levels of insulin, which often occurs in people with Type 2 diabetes who are insulin resistant, may accelerate heart failure when heart damage occurs. This current study clarifies what signals within the cell trigger this event. Specifically, insulin receptor substrate-1 (IRS1) is a protein required for insulin to transduce its signals to the rest of the cell. Another protein, IRS2, is equally expressed in heart muscle, but it was unclear whether IRS1 or IRS2 equally contributed to accelerating heart failure in insulin resistant states. The Abel laboratory created genetically engineered mice lacking either IRS1 or IRS2 in cardiac muscle cells and subjected these mice to a stress that induces heart failure, namely pressure overload. The IRS1-deficient mice were completely protected from heart failure in the face of this injury, while IRS2-deficient mice were not. Calling the IRS1 protein the “bad cop,” Abel explained their next task was then to uncover why, which led to two discoveries. “Number one,” he said, “IRS1 seems to drive inflammation in the heart. Number two, IRS1 suppresses a protective pathway in the heart called ‘signaling via cyclic GMP,’ which provides additional protection.” Another pair of signaling molecules were also identified in this recently published project, AKT1 and AKT2. Similarly, to their work with IRS1 and IRS2, the researchers identified another “bad cop” in the pair. Deletions of the AKT1 gene in mice also lacking IRS2, which led to worse heart failure, were protected from heart failure, when AKT1 levels were genetically reduced. Finally, human heart samples obtained at the time of left ventricle assist device-implantation surgeries in patients with heart failure—performed at the University of Utah—were compared with normal donor hearts. The Abel team found their results confirmed. Just as in the mice, the heart failure samples revealed hyperactivation of AKT1 and IRS1. Implications of the study point toward treatments for people with diabetes that also take the cardiac risk into account. “Therapies to treat people with diabetes at risk of heart failure should ideally seek to do so in ways that lower insulin levels,” Abel said. SGLT2 inhibitors, he explained, are the only class of diabetes treatment proven to consistently reduce the risk of heart failure. These also cause the kidney to excrete glucose, which in turn would lower circulating concentrations of insulin. “More attention to agents that might lower insulin levels might actually help to reduce the risk of heart failure in diabetes.” Contributors to this work, which was funded by the National Institutes of Health and the American Heart Association, include researchers from the University of Iowa, the University of Utah, the University of Alabama Birmingham, Harvard Medical School, and the University of California Davis. Related Articles DRC Director's Report - May 2020 Diabetes is a disease of uncontrollable high blood glucose. Insulin, the hormone that reduces blood glucose, is secreted from beta cells embedded in the pancreas in structures called islets. Although overnutrition has been blamed for the inability of beta cells to secrete enough insulin in type 2 diabetes, it has remained unclear how overnutrition causes beta cells to fail. This is a critical question to solve in order to develop effective therapy to protect beta cells in conditions of overnutrition and to cure type 2 diabetes. DRC Director's Report - June 2020 FOEDRC members Al Klingelhutz, PhD, Professor of Microbiology & Immunology and Radiation Oncology and James Ankrum, PhD, Assistant Professor of Biomedical Engineering, have received funding as part of the Iowa Superfund Research Program (ISRP). As co-directors of 1 of the 5 projects, “Role of Airborne PCBs in Adipogenesis, Adipose Function, and Metabolic Syndrome”, they will focus on how the environmentally prevalent toxin PCB ) (polychlorinated biphenyls) accumulation in fat affects the development of obesity, fatty liver disease, and type II diabetes. The ISRP, headed by Keri Hornbuckle, PhD, Professor of Civil and Environmental Engineering, will receive a total of $11.4 million over a 5-year period to continue its research on polychlorinated biphenyls, or PCBs, and the impact they have on human health. DRC Director's Report - January 2020 The New Year is a good time to reflect on our past progress and to look forward to research advances in the year to come. In this regard, the receipt of endowed chairs recognizes faculty whom we believe have established a track record of accomplishment and whose ongoing success will pave the way for the future of the FOEDRC. Therefore, we would like to recognize Dr. Sue Bodine, Dr. Ayotunde Dokun, and Dr. Kamal Rahmouni, the three newest recipients of endowed chairs from the Fraternal Order of Eagles Diabetes Research Center (FOEDRC). DRC Director's Report - April 2020 I am excited to report that Sam Stephens, PhD, Fraternal Order of Eagles Diabetes Research Center member, and Assistant Professor of Internal and Molecular Medicine was recently awarded a $1.2 million grant. The grant was awarded by the Congressionally Directed Medical Research Program (CDMRP), administered by the Department of Defense for diabetes research. DRC Director's Report - December 2018 As we come to the end of another successful year for the FOEDRC, I want to thank the FOE and my colleagues within the Diabetes Research Center for continuing to push the research boundaries to improve the lives of many who suffer from diabetes. On a personal note, I received a number of honors for my work this year including being asked to deliver the Presidential Lecture of the University of Iowa, receiving Fraternal Order of Eagles Humanitarian Award and the 2018 History Makers Award - the African American Museum of Iowa (AAMI). My receipt of this recognition is really a recognition of what you do and I consider myself very fortunate to lead such an outstanding organization. To close out the year I thought you might be interested in reading about some ways that our researchers are turning “fun and games” into a benefit for our patients with diabetes. DRC Director's Report - December 2018 As we come to the end of another successful year for the FOEDRC, I want to thank the FOE and my colleagues within the Diabetes Research Center for continuing to push the research boundaries to improve the lives of many who suffer from diabetes. On a personal note, I received a number of honors for my work this year including being asked to deliver the Presidential Lecture of the University of Iowa, receiving Fraternal Order of Eagles Humanitarian Award and the 2018 History Makers Award - the African American Museum of Iowa (AAMI). My receipt of this recognition is really a recognition of what you do and I consider myself very fortunate to lead such an outstanding organization. To close out the year I thought you might be interested in reading about some ways that our researchers are turning “fun and games” into a benefit for our patients with diabetes. Showing 0 Comment Comments are closed.