Véronique-Anne Lacombe, University of Oklahoma Health Sciences Center
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Le 09 June 2023Amphi DEfalse false
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11h30
Regulation of cardiac glucose transport by sarcoplasmic reticulum calcium handling: Novel therapeutic targets for diabetes
Regulation of cardiac glucose transport by sarcoplasmic reticulum calcium handling: Novel therapeutic targets for diabetes
Véronique-Anne Lacombe, DVM, PhD
Professor, Department of Physiological Sciences
College of Veterinary Medicine,
Oklahoma State University
Abstract
Diabetes, a worldwide epidemic disease, results from a defect of insulin production or action, with dysfunctional glucose transport into insulin-sensitive tissues (i.e., striated muscles and adipose tissues). Diabetes has been identified as a major risk factor for cardiovascular diseases, such as diabetic cardiomyopathy, heart failure and atrial fibrillation. We previously demonstrated that impaired sarcoplasmic reticulum calcium handling underlies diabetic cardiomyopathy. Although the heart is a major organ to utilize glucose, the regulation of glucose transport in the heart remains not well elucidated, especially in regard to insulin-independent pathway. Using transgenic mice overexpressing the sarcoplasmic reticulum calcium ATPase (SERCA) pump in the heart, we demonstrated that the SERCA pump is a major regulator of cardiac glucose transport by an AS160 dependent mechanism during healthy and insulin-deficient diabetic state. Surprisingly, cardiac-specific SERCA overexpression partially rescued hyperglycemia during diabetes by improving glucose transport in peripheral insulin-sensitive tissues. Using quantitative mass spectrometry and ELISA, we identified protein disulfide isomerase (PDI) to be upregulated in the heart and serum of transgenic healthy and diabetic mice. We further identified that PDI mediates the heart's ability to regulate whole body glucose metabolism. Insights gained from this study could identify the SERCA pump and PDI, a cardiac secretome, as novel therapeutic targets for diabetic patients.
Biography
Dr. Lacombe earned her DVM degree from the National Veterinary School of Maisons-Alfort. After completing a residency in large animal internal medicine at the Ohio State University College of Veterinary Medicine, she earned her PhD and then completed a postdoctoral fellowship at the Ohio State’s College of Pharmacy. Prior to joining Oklahoma State University, she was a Research Assistant Professor at the Ohio State’s College of Pharmacy. Dr. Lacombe is currently a Full Professor and the Director of the Comparative Metabolism Research Laboratory at Oklahoma State University. Her laboratory investigates glucose metabolism in insulin-sensitive tissue during pathophysiological conditions, using primarily small and large animal models of metabolic diseases (i.e., diabetes, obesity and insulin resistance). She is also an adjunct Professor at the University of Oklahoma Health Sciences Center, as well as an investigator of the Harold Hamm Diabetes Center and the Oklahoma Center for Respiratory & Infectious Diseases. Dr. Lacombe is the Chair of Veterinary Faculty Council and Vice-Chair of Graduate Council.
