UCSF DIABETES, ENDOCRINOLOGY & METABOLISM TRAINING PROGRAM FACULTY RESEARCH SUMMARIES

Our laboratory currently has three major areas of emphasis. The underlying theme of these seemingly diverse research programs is to understand the roles that signaling through the insulin receptor, and the closely related insulin-like growth factor, play in health and disease. In an ongoing clinical study, we are characterizing non-obese, otherwise healthy subjects who are insulin resistant, and thus at risk for the development of type 2 diabetes mellitus, cardiovascular disease and other components of the metabolic syndrome. In these subjects we are determining the extent to which impairments in insulin receptor function contribute to insulin resistance, the lifestyle and physiological factors that contribute to this condition, and the effectiveness of exercise training intervention to reverse defects in insulin signaling.

In the laboratory, we are studying the causes and consequences of lipid accumulation within muscle cells, which is associated with insulin resistance in our clinical study. It is our aim to determine the cause of impairments in fat metabolism that lead to lipid accumulation, as well as the mechanisms whereby intracellular lipids directly inhibit the insulin signaling pathway. In addition, we are exploring novel approaches to reducing cellular accumulation of lipids by targeting cellular carboxylation reactions that can regulate the capacity of muscle to oxidize fat.

Finally, we are studying the contribution of the insulin-like growth factor in breast and prostate cancer. By employing small molecule inhibitors of this receptor, we are exploring the manner in which the dependence of cancer cells on insulin-like growth factor for survival can be exploited as an anti-cancer therapy.

Selected Publications:

Evans, J, JF Youngren, ID Goldfine. Effective Treatments for Insulin Resistance: Trim the Fat and Douse the Fire. Trends in Endocrinology and Metabolism. 15:425-31, 2004.

Pender, C, ID Goldfine, J Kulp, CJ Tanner, BA Maddux, KG MacDonald, JA Houmard, JF Youngren. Analysis of Insulin-Stimulated Insulin receptor Activation and Glucose Transport in Cultured Muscle Cells from Obese Subjects. Metabolism. 54(5):598-603, 2005.

Youngren, JF, K Gable, C Penaranda, BA Maddux, M Zavodovskaya, M Lobo, M Campbell, J Kerner, ID Goldfine. Nordihydroguaiaretic Acid (NDGA) Inhibits the IGF-1 and C-Erbb2/Her2/Neu Receptors and Suppresses Growth In Breast Cancer Cells. Breast Cancer Res Treat. 94(1):37-46, 2005.

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