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TOPICAL COLLECTIONS

Novel and Traditional Approaches to Gauge Insulin Sensitivity and Signaling Aberration in Health and Disease

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Carolyn Ecelbarger

Carolyn Ecelbarger

Georgetown University, Division of Endocrinology and Metabolism, Department of Medicine

As a renal physiologist and nutritionist (PhD in Nutrition Sciences from the University of Wisconsin-Madison, 1992), Dr. Ecelbarger has focused heavily on regulating the kidney by insulin and in altered metabolic states, such as obesity type 1 and type 2 diabetes. She conducted a productive fellowship in 1992-1998 at the NIH in Dr. Mark Knepper’s Laboratory of Kidney and Electrolyte Metabolism. In 1998, she came to Georgetown University as an Instructor and is now a tenured Associate Professor in the Department of Medicine, the Division of Endocrinology and Metabolism. She has been funded as a Principal Investigator by the U.S. government via K01, R01, and R21 mechanisms, foundations, e.g., the American Diabetes Association, the American Heart Association, the National Kidney Foundation, as well as by industry. In the last 10 years, she generated several mouse lines with a renal-cell-specific knockout of the insulin receptor (Insr). She then expanded these studies to include knockout of the insulin-like growth factor receptor (Igfr1), the mammalian target of rapamycin (mtor), and microRNA 451, a microRNA with a putative role in diabetic nephropathy. Her several publications define the role of insulin signaling in the kidney. She is also developing high-throughput approaches, including searching for a panel of microRNA biomarkers to predict susceptibility to nephropathy in type 2 diabetes. As such, she is investigating human urine samples from the Family Investigation of Nephropathy and Diabetes (FIND study). In addition to research, Dr. Ecelbarger is a Georgetown University Faculty Senate member, the Institutional Animal Care and Use Committee, and the Ethics Committee at the Georgetown University Medical Center. She frequently hosts students of various levels, e.g., high school through a graduate-level in her laboratory. Dr. Ecelbarger, a mother of three, makes her home in Annandale, VA with her husband, Gary. In her free time, she enjoys reading and running.

Collection Overview

Insulin is vital for life itself, as are insulin receptors (InsR). Whole-body deletion of InsR was found to be incompatible with life. One of the principal known causes of glucose-homeostasis disorders is InsR resistance of major metabolic tissues, i.e., liver, adipose, and skeletal muscle. Insulin is required to transport glucose into the cells of these energy-generating and storage tissues, in the absence of which, hyperglycemia develops. In addition to these metabolic tissues, other major organs, e.g., kidney, brain, and heart express InsR. Some, such as the brain and heart rely on glucose as their major energy source, and in the kidney, insulin activates transporters and channels involved in the reabsorption and thus retrieval of vital filtered nutrients, electrolytes, and other substances, which would otherwise be lost in the urine. This Methods Collection is primarily aimed at reviewing the state-of-the-art approaches to quantitate and characterize InsR signaling and sensitivity in cells, tissues, organs, animal models, and humans. The plan for the collection of 5-8 units: 1) approaches and limitations to gauging insulin sensitivity in humans; 2) determining novel patterns of insulin targets using phosphoproteomics; 3) the use of cell- and tissue-select animal InsR knockout to elucidate the role of the insulin receptor; 4) newer imaging approaches to deduce insulin actions in the whole-organism; 5) insulin transcriptome; 6) genetics of insulin signaling and insulin resistance

Articles

Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance
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Differentiated Mouse Adipocytes in Primary Culture: A Model of Insulin Resistance

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2023

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