References:
- Knutson V. The Release of Lipoprotein Lipase from 3T2-L1 Adipocytes is regulated by Micro vessel Endothelial Cells in an insulin-Responsive Manner. Endocrinol. 141:693-701, 2000.
- Knutson V. Insulin-Induced in Situ Phosphorylation of the insulin receptor located in the Plasma Membrane Versus Endosomes. Biochem. Biophys. Res. Comm. 227:27-34, 1996.
- Knutson V. Introduction of Insulin Resistance in Cultured Adipocytes: Chronic Hyperinsulinemia Differentially Affects Insulin Signaling Pathways. In Vitro Cell. Dev. Biol. 33:77-81, 1996.
Victoria P. Knutson, Ph.D.
Associate Professor
UTHSC, Medical School, (713) 500 - 7450
Victoria.P.knutson@uth.tmc.edu
Signal transduction in diabetes
The binding of insulin to its specific, cell surface receptor initiates a myriad of cellular processes collectively termed insulin action. Our research focuses on the events which occur to the insulin receptor protein after it binds insulin. In particular, upon the short-term treatment with insulin, we are interested in the sub cellular components through which the receptor moves, and what covalent modifications occur to the receptor protein (phosphorylation/dephosphorylation of tyrosine and serine residues and receptor proteolysis) in these specific compartments. In addition, we are also interested in these same cellular events but under conditions of chronic, long-term incubation with insulin – conditions which mimic the state of insulin resistance found in patients with adult-onset diabetes mellitus. These studies have led us to investigate insulin action in fat cells, a common in vivo target of insulin. Our recent studies have led us to pathways, especially in states of malignant transformation, such as breast cancer. We are also interested in the insulin-induced regulation of lipoprotein lipase, an enzyme critical to the control of serum triglyceride levels, and how insulin resistance leads to the development of hyper-trigliceridemia and heart disease in diabetic patients.
Our work is very integrative and relies on all of the major disciplines of biomedical sciences. We utilize approaches characteristic of Cell Biology in defining the sub-cellular itinerary of the insulin receptor. We utilize he quantitative approaches characteristic of Biochemistry to define the rate of movement of the receptor and lipoprotein lipase from one site to another. We also utilize the approaches and techniques of Molecular Biology to over-or-under-express important effectors molecules in the signal transduction cascade.
