31 December DRC Director's Report - January 2021 December 31, 2020 By The Fraternal Order of Eagles Diabetes Research Center 0 A recent study by a team of UI researchers led by E. Dale Abel, MD, PhD, Director, FOEDRC discovered eating a ketogenic diet rescued mice from heart failure. The study, published in the November issue of the journal Nature Metabolism, was one of three companion papers from independent research teams that all point to the damaging effects of excess sugar (glucose) and its breakdown products on the heart. The UI study also revealed the potential to mitigate that damage by supplying the heart with alternate fuel sources in the form of high-fat diets. Given its need for a constant, reliable supply of energy, the heart is very flexible about the type of molecules it can burn for fuel. Most of the heart’s energy comes from metabolizing fatty acids, but heart cells can also burn glucose and lactate, and also ketones. Too much glucose, however, has been linked to heart failure, and heart failure is a leading cause of death in people with Type 2 diabetes. Heart biopsies from people with heart failure show an accumulation of sugar molecules in the heart, suggesting that this “backup” of glucose, because it is incompletely metabolized, may be contributing to the damage. The new UI study investigated how glucose and accumulation of these metabolites contribute to heart failure. UI researchers removed a critical protein from heart cells in mice. This protein, called the pyruvate carrier protein, is responsible for taking pyruvate, derived from glucose metabolism, into mitochondria where it's further metabolized to make energy. Levels of this protein are reduced in human failing hearts. Removing the pyruvate carrier protein prevents heart cells from using glucose as an energy source and causes a backup of the glucose-derived molecules, similar to what has been seen in human heart failure. “We found that this was sufficient to cause these mouse hearts to fail,” Abel explains. “If you block this fundamental process of pyruvate uptake for energy, the unused glucose leaks into other metabolic pathways that lead to cell death and damage and contributes to heart failure. It's really another way of saying that too much sugar is bad for the heart.” There has been a long and controversial history of studies that counterintuitively suggest that high-fat diets may be beneficial to the heart. As this evidence has built up, there has been a growing interest in testing the effects of ketogenic diets in patients with heart failure, and several clinical trials are ongoing. The UI study used mice to investigate what happened when the mouse hearts that could not process glucose were provided with fats or ketones for energy instead. The researchers found that ketogenic feeding (a high-fat, low-carbohydrate, low-protein diet) completely prevented heart failure and normalized heart function in diabetic mice. In addition, feeding the mice either ketones alone, or a high-fat diet that was not ketogenic, also rescued failing hearts. Overall, the study suggested that shutting down the glucose overload by any means was beneficial. “There's something about too much glucose that appears to be very harmful,” says Abel. The study doesn’t directly address whether this finding is relevant to heart failure in human patients, and if there are risks versus benefits to the heart of these high-fat diets. Abel says the study findings do not mean that patients with heart failure should start eating a keto diet. “What I can say is that other studies have shown that when the heart begins to fail, it tends to want to use more ketones. So, it may be feasible that the heart uses ketones to try and rescue the failing heart,” he says. “Studies like ours really add impetus to the current clinical trials of ketogenic feeding in people with heart failure.” Abel worked with a multidisciplinary team of UI researchers from the Fraternal Order of Eagles Diabetes Research Center and the Abboud Cardiovascular Research Center, as well colleagues from the University of Montreal in Canada, the University of Minnesota, the University of Utah, and The Ohio State University. The research was funded in part by grants from the National Institutes of Health, the American Heart Association, the American Diabetes Association, and Montreal Heart Institute Foundation. Related Articles DRC Director's Report - January 2019 The new year is always a time to look back and reflect on the many achievements of the prior year. I have been pleased that the Fraternal Order of Eagles has committed continued support to a program that will be overseen by the FOEDRC that seeks to develop new treatments for diabetes and its complications and to bring them ultimately to market. The Bridge to the cure program represents an innovative collaboration and we are excited by what this new year will bring. For this reason, I have chosen to write about one example from a FOEDRC member that recently demonstrated the ability of the compound nicotinamide riboside to restore nerve damage from chemotherapy. We believe that this same mechanism could lead to improved nerve function in people with diabetes. I hope that you will enjoy reading about this exciting advance below. 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 - 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. DRC Director's Report - November 2018 We have known for a very long time that obesity is associated with many cardiovascular and metabolic diseases. Type 2 diabetes, fatty liver disease (where liver stores fat in large lipid droplets), coronary artery disease, heart failure, and many more chronic diseases are all linked to obesity. DRC Director's Report - March 2019 Brian T. O’Neill, MD, PhD, assistant professor in the Division of Endocrinology in the Department of Internal Medicine and member of the FOEDRC recently published in the journal Diabetes the discovery that FoxO proteins, which are transcription factors that regulate DNA, are the critical regulators of diabetes-related muscle atrophy. Showing 0 Comment Comments are closed.