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.
Bonini
J A
JA
Department of Molecular and Cellular Biochemistry, Loyola University of Chicago, Maywood, IL 60153, USA.
Colca
J
J
Hofmann
C
C
D019870:1-Phosphatidylinositol 4-Kinase; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D051380:GRB2 Adaptor Protein; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism; D008297:Male; D015513:Oncogene Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495950:Grb2 protein, rat; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C078332:Nck protein; D015513:Oncogene Proteins; D010750:Phosphoproteins; D011506:Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase; D011972:Receptor, Insulin; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516727:Ptpn11 protein, rat; C509250:Ptpn6 protein, rat