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 - July 2021 The Spring 2021 issue of the Carver College of Medicine Magazine “Medicine at Iowa”, circulated to all UI alumni, featured an important serendipitous breakthrough by scientists at the University of Iowa Fraternal Order of Eagles Diabetes Research Center (FOEDRC). FOEDRC scientists discovered at safe new way to manage blood sugar non-invasively with electromagnetic fields (EMFs). This discovery could have major benefits in diabetes care, particularly for patients whose current treatment plan is cumbersome and involves checking their blood sugar multiple times daily with finger sticks. DRC Director's Report - April 2021 FOEDRC member Matthew Potthoff, Ph.D., Associate Professor of Neuroscience and Pharmacology, and graduate student Sharon Jensen-Cody recently wrote a review article entitled: “Hepatokines and metabolism: Deciphering communication from the liver” that was published in the Journal Molecular Metabolism. This article was featured on the cover of the February issue of the Journal, that increased the visibility of their work. DRC Director's Report - March 2021 This month, the Spring 2021 issue of the Iowa Magazine devoted its cover and featured the University of Iowa Fraternal Order of Eagles Diabetes Research Center (FOEDRC). The heartwarming article shares real life testimonies of diabetic individuals, cared for at the University of Iowa and the impact of diabetes on their daily life. The desire for relief is real and certainly not lost on physicians and scientists at the FOEDRC. The Center’s mission is to improve the lives of individuals with the disease and find a cure. Every day dedicated FOEDRC scientists conduct a wide range of research projects to improve and benefit the lives of many. DRC Director's Report - May 2021 Obesity has reached epidemic proportions in the US and around the world. This is a problem because being obese increases the likelihood of developing serious medical problems such as type 2 diabetes, high blood pressure and cardiovascular diseases such as heart attacks and heart failure. Obesity also increases the risks of complications from COVID-19 infections. We still do not understand all of the reasons why obesity develops and why some people develop complications and others do not. In work recently published in the Journal Molecular Metabolism, FOEDRC member Dr. Kamal Rahmouni, PhD, professor of Neuroscience, Pharmacology, and Internal Medicine, in collaboration with FOEDRC colleagues at the University of Iowa, identified a protein complex, called the BBSome. These are present in neurons (nerve cells) in a part of the brain called the hypothalamus. DRC Director's Report - June 2021 Pancreatic beta cells are only cells that can make insulin in humans. In type 2 diabetes, pancreatic beta cells are damaged and cannot make sufficient insulin to keep blood glucose levels normal. As overnutrition and obesity is a well-known risk factor for type 2 diabetes, it is important to find a way to protect beta cells from over nutrition. In a recently published study in the scientific journal JCI Insight, led by Dr. Yumi Imai, Associate Professor of Internal Medicine and member of the FOEDRC, her laboratory has discovered that a protein known as Perilipin 2 plays an important role in protecting beta cells under nutritional challenge. 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. Showing 0 Comment Comments are closed.