ALTERED EXPRESSION OF INSULIN SIGNALING COMPONENTS IN STREPTOZOTOCIN-TREATED RATS

Insulin signaling is known to proceed through the insulin receptor to the insulin receptor substrate-1 (IRS-1). Tyrosine-phosphorylation of IRS-1 causes it to associate with the src-homology-2 (SH2) domains of at least four other proteins: phosphatidylinositol 3'-kinase (PI3K), growth factor receptor-bound protein-2 (GRB2), Nck, and Syp. In order to understand the cellular derangements associated with type I diabetes, the levels of these four SH2-containing proteins was determined in streptozotocin-induced diabetic rats. In liver tissue of diabetic rats, the levels of Nck and Syp were significantly decreased to 71+/-6% and 61+/-4% control, respectively, while in fat tissue only the Syp levels were significantly reduced to 72+/-9% control. PI3K levels were higher in livers of diabetic rats than controls, but unchanged in fat. The insulin-deficient diabetic condition was thus associated with altered levels of insulin signaling components. (C) 1995 Academic Press, Inc.