Contact Info Ira Goldfine, MD Endocrinology/Metabolism 1600 Divisadero St., MZ C431, Box 1616 San Francisco, CA 94143-1616 Ph: (415) 885-7429 Fax: (415) 885-3787   Email: ira.goldfine@ucsf.edu

Professor in Residence

My diabetes research concerns the transmembrane signaling mechanisms for the insulin receptor and related receptors and why insulin receptor signaling is defective in type 2 diabetics. We are carrying out clinical studies to understand the cellular defects in insulin action that exist in insulin resistant non-diabetic subjects and type 2 diabetics. In addition, we are investigating the effects of exercise training, antioxidants, and new anti-diabetic drugs in these individuals. In the laboratory we are investigating insulin receptor tyrosine kinase inhibitors, in particular membrane glycoprotein PC-1, an inhibitor of insulin signaling in insulin resistant patients. A second area of laboratory investigation is an analysis of the three dimensional structure of the insulin receptor by employing the scanning electron microscope. A third project in the laboratory is the development of small molecule, insulin receptor activators for eventual use diabetic patients. A fourth area is the development of small molecule inhibitors of the IGF-1 receptor to treat breast and other cancers.
 
Selected Publications:
 
BA Maddux, P Sbraccia, S Kumakura, S Sasson, J Youngren, A Fisher, S Spencer, A Grupe, W Henzel, TA Stewart, GM Reaven, ID Goldfine.  Membrane Glycoprotein PC-1and insulin resistance in non-insulin-dependent diabetes.  Nature 373:448-451, 1995.
 
BA Maddux and ID Goldfine.  Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha subunit.  Diabetes 49:13-19, 2000.

Maddux B, Chang Y-N, Accili D, McGuinness OP, Youngren JF, Goldfine ID. Overexpression of the insulin receptor inhibitor PC-1/ENPP1 induces insulin resistance and hyperglycemia. Am J Physiol Endocrinol Metab. In Press, 2006.
 
Pender C, Goldfine ID, Manchem VP, Evans JL, Spevak WR, Shi S, Rao S, Bajjalaeih S, Maddux BA, Youngren JF. Regulation of insulin receptor function by a small molecule insulin receptor activator. J Biol Chem. 277: 43565-71, 2002.

Youngren J, Gable K, Peñaranda C, Maddux B, Zavodovskaya M, Lobo M, Campbell M, Goldfine ID. Nordihydroguaiaretic Acid (NDGA) Inhibits the IGF-1 and C-Erbb2/Her2/ Neu Receptors And Suppresses Growth in Breast Cancer Cells. Breast Cancer Research Treatment. 94 (1):37-46, 2005.