Fraternal Order of Eagles Diabetes Research Center Announces New Grant Recipients (September 2016)

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 sixth 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 and represent 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 30 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. However, a first for the Center, the committee unanimously identified one additional proposal that will receive $20,000 to support their research proposal for one year. We are pleased to have identified the resources to fund this fourth meritorious proposal. The 2016-2017 recipients are:

Ryan L. Boudreau, PhD
Assistant Professor, Department of Internal Medicine – Cardiovascular Medicine
Project Title: “Defining the Role of a Novel Mitochondrial Protein in Metabolism”

Boudreau Project Summary
The metabolic syndrome and associating health problems (e.g. obesity, diabetes and cardiovascular disease) are leading causes of morbidity and mortality worldwide, warranting further investigation of disease mechanisms and advanced therapies. Although food overconsumption and lack of exercise are key factors contributing to the metabolic syndrome, disease onset and progression are shaped by a host of other environmental and genetic influences. Together, these impact a breadth of cellular and whole-body metabolic functions, for example, how our cellular “metabolic factories,” known as mitochondria, utilize nutrients to produce energy. In addition to their roles in metabolism, these cellular organelles are critical regulators of cell stress and death responses, and it is well-established that mitochondrial dysfunction underlies the development of the metabolic syndrome. Thus, improving our understanding of how mitochondria work will unveil opportunities to advance the prevention, diagnosis and treatment of metabolic disease. Here, we propose studies to characterize a novel mitochondrial protein that we have recently discovered and named “mitoregulin”. We will manipulate this protein (i.e. add more of it or take it away) in cell culture models and in mice to determine the impact on mitochondrial function and readouts of whole-body metabolism. We anticipate that our experimental results will highlight the biological importance of this novel protein in mitochondrial metabolism, supporting follow-up investigations of mitoregulin’s role in disease models of obesity and diabetes. Overall, these studies will refine our knowledge of mitochondrial biology, particularly as it pertains to metabolic-related diseases, perhaps pointing to mitoregulin as a new therapeutic target for their treatment.

Brandon S. Davies, PhD
Assistant Professor, Department of Biochemistry
Project Title: “Skeletal Muscle Programming of Capillary Endothelial Cells”

Davies Project Summary
Dietary fat is an important energy source for many tissues including heart, skeletal muscle, and brown adipose tissue. Fat also plays a key role in the development of metabolic disorders including obesity, metabolic syndrome, and type 2 diabetes. Inappropriate delivery of fat (i.e. too much to one tissue, too little to another) is a hallmark of many of these metabolic disorders. In order for fat to be delivered to tissues, it must first pass through the blood vessel wall. The endothelial cells that form the vessel walls in fat-utilizing tissues play several important roles in regulating fat delivery, and must be programmed to express the proteins necessary to perform these roles. How this programming takes place is not known. The goal of our research is to determine how the tissues that use fat program their capillary endothelial cells to process and deliver fat from the bloodstream. In these studies we will use expression of GPIHBP1 as a surrogate marker for the capillary endothelial cells that are competent to deliver fat. GPIHBP1 is a critical part of the fat delivery process and we have previously shown that it is expressed only in the capillaries of tissues that use dietary fat. We have recently found that muscle cells secrete a signal that turns on the expression of GPIHBP1 in capillary endothelial cells. The studies proposed in this application will expand on this discovery by carefully characterizing this signaling and by identifying the signal molecule. Completing these aims will greatly enhance our understanding of how different tissues control the import of fat from the bloodstream. In turn, this enhanced understanding may allow the development of novel therapeutic approaches that modulate the delivery of dietary fat in order to treat metabolic disease. 

Eric B. Taylor, PhD
Assistant Professor, Department of Biochemistry
Project Title: “A novel regulator of glutamine-driven gluconeogenesis”

Taylor Project Summary
We are interested in understanding the role of glutamine-driven gluconeogenesis in type 2 diabetes (T2D). Multiple lines of evidence suggest this is a clinically important feature of T2D. However, the mechanisms regulating glutamine-driven gluconeogenesis are not well understood. We have identified a poorly annotated protein important for glutamine-driven mitochondrial respiration and gluconeogenesis. We seek pilot funding to determine the biochemical activity of this protein, the mechanisms underlying its role in glutamine-driven gluconeogenesis, and how its function contributes to hyperglycemia during T2D. We expect this pilot effort will support a quality publication and a competitive national-level grant proposal.

Wei Bao, MD, PhD
Assistant Professor, Department of Epidemiology
Project Title: “Nontraditional glycemic markers in early pregnancy as predictors of gestational diabetes”

Bao Project Summary
Gestational diabetes mellitus (GDM) is a common pregnancy complication that affects ~9% of all pregnancies in the United States. GDM is usually diagnosed at 24-28 weeks of gestation by measuring fasting and post-load glucose in an oral glucose tolerance test (OGTT). Since GDM is associated with adverse health outcomes in the fetus and children, early prediction of GDM is imperative. However, the utility of glucose in early pregnancy for GDM prediction is limited because fasting glucose and OGTT are usually not available at that time. Using non-fasting blood glucose for GDM prediction is problematic due to the substantial glucose variability influenced by food intake. Nontraditional glycemic markers, including fructosamine, glycated albumin, and 1,5-anhydroglucitol (1,5-AG), do not require fasting; therefore they are perfect fit to the current clinical practice and can be measured in the same blood samples collected in early pregnancy for other routine lab tests. We propose to conduct a nested case-control study in a prospective cohort of pregnant women. In this pilot study, we will measure nontraditional glycemic markers in first-trimester maternal plasma samples of pregnant women, and associate these markers with the risk of incident GDM. Moreover, we will assess the utility of these markers in the discrimination and prediction of GDM, as indicated by improved C-statistic and reclassification measures. Previous studies on the use of these markers for GDM prediction mainly used blood samples collected at the time of GDM diagnosis and the results have been conflicting. The proposed study is innovative because it represents a departure from the status quo by examining nontraditional glycemic markers in early pregnancy as early predictors for GDM. If successful, the proposed study may change the clinical paradigm in the screening and prediction of GDM. Findings from this study will be important to develop Specific Aims for subsequent NIH R01 projects that integrate multiple biochemical and genetic markers for improved GDM prediction in the era of “Precision Medicine”.

The projects of the three investigators funded by the Fraternal Order of Eagles endowment last year will also be supported for a second year. The investigators are:

Aloysius (Al) Klingelhutz, PhD
Associate Professor, Department of Microbiology and Radiation Oncology
Project Title: “Role of Aryl Hydrocarbon Receptor in Adipogenesis and Diabetes”

Matthew Potthoff, PhD
Assistant Professor, Department of Pharmacology
Project Title: “Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver”

Peter M. Snyder, MD 
Professor, Department of Internal Medicine – Cardiovascular Medicine and Molecular Physiology & Biophysics
Project Title: “Epithelial Na+ Channel Regulation by Glucose”

Congratulations to all of our FOEDRC Pilot & Feasibility Grant Award Recipients!

Tuesday, September 13, 2016