Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Kahn, Barbara B.
Location Harvard University
Primary Field Medical Physiology and Metabolism
Secondary Field Physiology and Pharmacology
 Election Citation
Kahn is a leader in defining mechanisms of glucose homeostasis and energy balance. She has shown how glucose transport/metabolism in adipocytes serves as an important regulatory event by stimulating release of novel molecules that affect insulin sensitivity in other tissues. This work provides fundamental insights into the pathogenesis of diabetes.
 Research Interests
My lab investigates the cellular and molecular mechanisms for insulin resistance in obesity and Type 2 diabetes. Our work established the critical role of the GLUT4 glucose transporter in adipocytes in regulating systemic insulin sensitivity, energy balance and inflammation. We showed that down-regulation of GLUT4 in adipocytes markedly increases the risk for Type 2 diabetes and GLUT4 overexpression in adipocytes enhances glucose tolerance. We use genomic, metabolomics and lipidomic approaches in human tissues and genetically-engineered mouse models to discover novel adipocyte-associated molecules. This has revealed important biomarkers and mechanisms for insulin resistance and diabetes. For example, we demonstrated that retinol-binding-protein-4 levels are elevated in insulin-resistant people and this causes insulin resistance by activating both innate and adaptive immune responses in adipose tissue. We also showed that de novo lipogenesis in adipocytes has a major role in regulating systemic insulin sensitivity. With Alan Saghatelian, we used global lipidomics to discover a novel class of lipids made in mammalian tissues, which correlate highly with insulin sensitivity in humans and have anti-diabetic and anti-inflammatory effects. We are investigating the receptors/signaling pathways by which these lipids enhance insulin secretion and insulin action, and determining the biosynthetic and degradative enzymes that regulate these lipids. A major goal is to discover new approaches to prevent and treat diabetes.

 
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