Candidate: The candidate, Leigh Perreault, MD, is a board-certified internist and endocrinologist with experience in epidemiologic, basic science, and clinical research spanning the past decade. Her most recent work examining gender differences in insulin action following acute exercise was supported by an Award from the Endocrine Fellows Foundation. This project has yielded novel and important differences which have layed the foundation for continuing research in the area exercise fuel metabolism as it pertains to insulin action. Without reservation, the most outstanding career goal is for the candidate to achieve excellence as an independent physician-scientist. The Mentored Patient-Oriented Research Career Development Award would provide the necessary training to pursue and achieve this goal. Career Development: The training plan consists of two primary elements: 1) the acquistion of an impressive number of new research skills via the local mentors as well as three scheduled apprenticeships away; and 2) educational activities, including formal classroom work, as well as attendance and participation in national meetings, local seminars and journal clubs, and one-on-one mentor interactions. Research Plan: The overall aim of the proposed project is to delineate gender differences in the development of insulin resistance in skeletal muscle. Understanding such differences would help expand our knowledge of the pathophysiology of insulin resistance itself, as well as aid in the targeting of insulin sensitizing therapy. The general hypothesis is that men and women with impaired glucose tolerance (IGT) develop insulin resistance in skeletal muscle through different mechanisms. Specifically, we hypothesize that this occurs via decreased oxidative capacity in women, and decreased action of peroxisome proliferatoractivated receptor (PPAR) alpha (and its target genes) in men. Furthermore, exercise training in women, and fibrate therapy in men, will attenuate these derangements. State-of-the-art tecnhiques will be imployed. Environment: The environment for the candidate's training is exceptional. The mentor, Robert H. Eckel, MD, is an international expert in the area of insulin action and substrate uptake and, furthermore, is a proven mentor. The co-mentor, Christopher A. DeSouza, PhD, is a rising star in academic research with expertise in exercise and substrate use. Collectively, the mentors, collaborators, and institutional commitment excels.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23DK064811-05
Application #
7391526
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2004-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2010-03-31
Support Year
5
Fiscal Year
2008
Total Cost
$158,490
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Bergman, B C; Hunerdosse, D M; Kerege, A et al. (2012) Localisation and composition of skeletal muscle diacylglycerol predicts insulin resistance in humans. Diabetologia 55:1140-50
Færch, Kristine; Bergman, Bryan; Perreault, Leigh (2012) Does insulin resistance drive the association between hyperglycemia and cardiovascular risk? PLoS One 7:e39260
Bergman, Bryan C; Perreault, Leigh; Hunerdosse, Devon et al. (2012) Novel and reversible mechanisms of smoking-induced insulin resistance in humans. Diabetes 61:3156-66
Perreault, Leigh; Bergman, Bryan C; Hunerdosse, Devon M et al. (2011) Fenofibrate administration does not affect muscle triglyceride concentration or insulin sensitivity in humans. Metabolism 60:1107-14
Perreault, Leigh; Bergman, Bryan C; Hunerdosse, Devon M et al. (2010) Altered intramuscular lipid metabolism relates to diminished insulin action in men, but not women, in progression to diabetes. Obesity (Silver Spring) 18:2093-100
Bergman, Bryan C; Perreault, Leigh; Hunerdosse, Devon M et al. (2010) Increased intramuscular lipid synthesis and low saturation relate to insulin sensitivity in endurance-trained athletes. J Appl Physiol (1985) 108:1134-41
Perreault, Leigh; Bergman, Bryan C; Hunerdosse, Devon M et al. (2010) Inflexibility in intramuscular triglyceride fractional synthesis distinguishes prediabetes from obesity in humans. Obesity (Silver Spring) 18:1524-31
Bergman, Bryan C; Perreault, Leigh; Hunerdosse, Devon M et al. (2009) Intramuscular lipid metabolism in the insulin resistance of smoking. Diabetes 58:2220-7
Perreault, Leigh; Bergman, Bryan C; Playdon, Mary C et al. (2008) Impaired fasting glucose with or without impaired glucose tolerance: progressive or parallel states of prediabetes? Am J Physiol Endocrinol Metab 295:E428-35