The Fraternal Order of Eagles Diabetes Research Center at the University of Iowa Carver College of Medicine is pleased to announce the results of its eighth round of pilot and feasibility research grants. These grant awards fund innovative pilot projects by early career investigators who are entering the diabetes research field, or established investigators with innovative ideas that focus their research program in a new direction that addresses important questions in diabetes research. The goal of the program is to generate data that will enable awardees to compete for peer-reviewed national funding for projects that show exceptional promise. These pilot project research grants are supported by gifts from the Fraternal Order of Eagles, which now endow this grant program.
A total of 27 researchers from across the UI campus submitted meritorious proposals that underwent a comprehensive two-stage review. The review panel had a challenging time to identify three proposals for funding from such a competitive field. Three applicants were selected to receive $50,000 to support their research proposal, with the possibility for a second year of funding, for a total of $100,000 over a two-year period.
The 2018 – 2019 recipients are:
Chad Grueter, PhD
Assistant Professor, Internal Medicine – Cardiovascular Medicine
Project Title: “Nuclear Regulation of Mitochondria”
The primary cause of mortality in patients with type II diabetes is heart disease. Both obesity and type II diabetes are risk factors for developing heart disease. They represent major health concerns that are rapidly growing in today’s society resulting in significant health and economic consequences. The current proposal addresses the impact of cardiac transcriptional and metabolic alterations that occur in both human and rodent models of diabetic cardiomyopathy. This proposal, if successful, will provide innovative insight into the dual regulation of transcription and metabolism by Cyclin C in the heart in obesity and type II diabetes. Importantly, the information gained from the studies on the heart will also provide the foundation for future studies in other cell types with significant alterations in metabolic gene expression and mitochondrial pathophysiology. This will provide a novel signaling pathway for developing therapeutics to target stress responsive mechanisms in type II diabetes.
Julien Sebag, PhD
Assistant Professor, Molecular Physiology and Biophysics
Project Title: “Development of small molecule enhancers of Insulin-stimulated GLUT4 translocation for the treatment of insulin resistance and type 2 diabetes”
Insulin secretion triggers the uptake of glucose from the blood to the tissues where it is stored. This process is essential to maintain a normal circulating glucose concentration. Several factors including obesity can contribute to the impairment of this process and render insulin less efficient at mediating glucose uptake. This is referred to as insulin resistance. The transport of glucose from the blood to the tissues (skeletal muscle and adipose tissue) is mediated by the GLUT4 glucose transporters, which are retained within the cells in the absence of insulin and moved to the surface of muscle and fat cells in response to insulin to allow glucose uptake. Increasing the efficiency with which insulin promotes the translocation of GLUT4 from intracellular stores to the cell surface has the potential to correct insulin resistance and protect from type II diabetes. Although this concept is well accepted, identifying molecules able to enhance insulin’s activity has been challenging due to the technical difficulty associated with measuring GLUT4 translocation. We have developed a novel high throughput GLUT4 translocation assay and screened a 50,000 molecule library to identify insulin sensitizers. We have also generated a new mouse model using the same technology to measure GLUT4 translocation in-vivo. We propose to improve upon the effect of the molecules identified by testing closely related compounds. We will then test the most promising molecules on mouse models of insulin resistance to identify molecules with in vivo activity. The goal is to generate lead compounds for the development of a novel type of drug to treat insulin resistance and type II diabetes.
Long Sheng-Song, MD, MS
Professor, Internal Medicine – Cardiovascular Medicine
Project Title: “Metabolic regulation of junctophilin-2”
Obesity is a major problem globally and increases the risk of developing a wide range of diseases including insulin resistance, type 2 diabetes and cardiovascular disease. The mechanism underlying the pathogenesis of obesity is still incompletely understood. Ca2+ ions are important for a variety of cellular signaling events and affects almost every aspect of cells. Early work in the late 80s and 90s has indicated that changes in intracellular Ca2+ concentrations in adipocytes are related to insulin resistance. However, to date, it remains poorly understood how Ca2+ is regulated in adipocytes, and how disturbed Ca2+ homeostasis contributes to obesity and obesity-associated pathologies, including insulin resistance and type 2 diabetes. In this proposal, we will use our established expertise in high resolution Ca2+ imaging and unique, genetically modified mouse models to answer these understudied yet fundamental questions. Upon successful completion of this project, we will establish a mechanistic understanding of the physiological regulation of Ca2+ homeostasis in adipocytes and the pathophysiological role of Ca2+ dysregulation in obesity-associated diseases. Building upon the exciting preliminary data from our lab, we expect to advance our knowledge by revealing a novel molecular mechanism of obesity-associated insulin resistance. New results generated through this project will provide critical preliminary data for submission of a highly competitive R01 application.