3 April FOE DRC Investigators Continue To Excel In Research April 3, 2018 By The Fraternal Order of Eagles Diabetes Research Center 0 Faculty members in the FOEDRC continue to excel in their ability to obtain competitive extramural funding for their research projects. In this month’s newsletter I will highlight new grant awards obtained by two of our members and next month I will feature another two. Dr. Julien Sebag, Assistant Professor of Molecular Physiology and Biophysics and member of the FOEDRC was recently awarded a 5-year $1.9M grant from the NIDDK for a project entitled: Investigating the requirement of MRAP2 for ghrelin function. The project studies the “hunger hormone” ghrelin, which is mainly secreted by the stomach during periods of fasting to signal hunger to the brain. Ghrelin regulates food intake and energy expenditure by acting at its receptor the Growth Hormone Secretagogue Receptor 1a (GHSR1a). The effect of ghrelin on food intake and energy homeostasis are mediated centrally in the hypothalamus, through the activation of the hunger sensing AGRP/NPY neurons. Genetic models that lack GHSR1a in all cells or in the hypothalamus are protected from diet-induced obesity. Thus, GHSR1a is a promising target for the treatment of obesity and blockers of the ghrelin receptor have been developed for this purpose. However, these drugs bind to receptors in multiple organs and are not very well absorbed, representing challenges which have precluded them from being used in the clinic. New compounds with improved chemical properties and better in-vivo efficacy could likely be identified by using more relevant drug discovery strategies. Improvement of screening strategies requires a better understanding of GHSR1a regulation. Dr. Sebag’s laboratory recently discovered that the hunger effect of ghrelin is lost in mice in which the Melanocortin Receptor Accessory Protein 2 (MRAP2) was genetically removed. Early studies demonstrate that MRAP2 interacts with GHSR1a and strongly increases its activity. Additionally, they showed that MRAP2 is expressed in the ghrelin responsive AGRP/NPY neurons. Consistent with those findings, Sebag and colleagues found that AGRP neurons from MRAP2 deficient mice fail to activate in response to fasting. The goals of the proposed project are to identify the role of MRAP2 in promoting ghrelin signaling and the response of AGRP neurons to starvation. The project also seeks to understand the molecular mechanisms through which MRAP2 enhances the efficacy of GHSR1a signaling. Successful completion of the proposed project will provide fundamental information on the role and mechanism of action of MRAP2 in AGRP neurons as it pertains to ghrelin functions. It will also advance our understanding of AGRP neuron regulation and the hypothalamic control of energy homeostasis. This research will generate new knowledge on the regulation of hormone receptors by accessory proteins and identify MRAP2 as a novel energy sensor. The knowledge derived from the proposed experiments will likely enable the design of more physiologically relevant model systems for drug discovery strategies targeting ghrelin signaling. It is anticipated that successful completion of these studies may lead to new and better drug treatments for obesity. Congratulations Julien! Also, kudos to Dr. Ethan Anderson, Associate Professor of Pharmacology and member of the FOEDRC and Dr. Jon Doorn, Associate Professor of Pharmacology for their recent award of a 2-year $425,000 grant from the NIH for a project entitled: Toxic Neurotransmitter Metabolites in Aged and Diabetic Myocardium. Atrial fibrillation (AF), an irregular heartbeat occurring in the upper compartments of the heart, is a chronic and debilitating cardiovascular disease that commonly occurs in aged and diabetic individuals. This project seeks to test a completely new theory that reactive molecules derived from the metabolism of norepinephrine and dopamine may be toxic to the heart, and also seeks to develop a sensitive way of measuring these molecules in blood samples. We expect that this knowledge and new technology may ultimately pave the way toward development of new treatments and screening methods for AF, and perhaps other cardiovascular disorders that are common to aged and diabetic individuals. Related Articles DRC Investigators Continue To Excel In Research DRC Director's Report - May 2018 This month I feature two additional grant awards that have been received by faculty members in the FOEDRC. Dr. Lira Vitor, Assistant Professor in Health and Human Physiology and member of the Fraternal Order of Eagles Diabetes Center and the Obesity Research and Education Initiative at the University of Iowa, received an American Heart Association (AHA) Scientist Development Grant. This 3-year $308,000 award is for a project entitled, Molecular insights into the exercise-mediated protection against diabetic cardiomyopathy. American Diabetes Association Supports FOEDRC Researchers DRC Director's Report - January 2018 Three researchers from the FOEDRC received new grants from the American Diabetes Association for groundbreaking research. The ability of our members to receive these competitive awards is truly remarkable and underscores the quality and rigor of the research that is being conducted in the FOEDRC. There are few institutions that received multiple awards in this current round of ADA funding. The awards to Drs. Ling Yang, Rajan Sah and Adam Rauckhorst are summarized below. DRC Researchers Publish Major Breakthrough In Understanding How Diabetes Induces Eye Damage In the retina, diabetes damages nerves before it damages blood vessels. Diabetes is a major risk factor for severe vision loss and blindness. A condition known as retinal diabetic neuropathy causes visual impairment through the degeneration of small nerves (neurons) in light-sensitive tissue called the retina, which lines the back of the eye. FOEDRC Continues To Lead In Studies Increasing Our Understanding of FGF21 DRC Director's Report, July 2017 As diabetes researchers work to identify potential new treatments for diabetes, colleagues at the FOEDRC continue to advance our understanding of how newly discovered hormones might work in ways that may lead to new ways to treat and prevent obesity and diabetes. One such hormone is fibroblast growth factor 21 (FGF21). Dr. Matthew Potthoff recently showed in mice that this hormone critically regulates the “sweet tooth” in mice. In a recent follow up study with collaborators from Denmark and published in the Journal Cell Metabolism, it is now confirmed that FGF21 also regulates sweet preference in humans. Now, Dr. Potthoff’s team has solved another piece of the puzzle by showing how and where FGF21 might act to regulate the body’s metabolism. DRC Researcher Chris Adams Develops New Therapy for Age-Related Muscle Atrophy Scientists at the FOE Diabetes Research Center and University of Iowa have discovered the first example of a protein that causes muscle weakness and loss during aging. The protein, ATF4, is a transcription factor that alters gene expression in skeletal muscle, causing reduction of muscle protein synthesis, strength, and mass. The UI study also identifies two natural compounds, one found in apples and one found in green tomatoes, which reduce ATF4 activity in aged skeletal muscle. Adams Named Fraternal Order of Eagles Diabetes Research Chair Christopher Adams, MD, PhD, has been named the Fraternal Order of Eagles Diabetes Research Chair. This position has been endowed by the Fraternal Order of Eagles (FOE) to propel and accelerate the pace of discoveries in the FOE Diabetes Research Center (FOEDRC), whose mission is to advance knowledge of the mechanisms of diabetes and its related complications through cutting-edge research. Showing 0 Comment Comments are closed.