Avtor/Urednik		Janež, Andrej; Worrall, Dorothy Sears; Olefsky, Jerrold M
Naslov		Insulin-mediated cellular insulin resistance decreases osmotic shock-induced glucose transport in 3T3-L1 adipocytes
Tip		članek
Vir		Endocrinology
Vol. in št.		Letnik 141, št. 12
Leto izdaje		2000
Obseg		str. 4657-63
Jezik		eng
Abstrakt		Similar to insulin, osmotic shock treatment of 3T3-L1 adipocytes causes translocation of GLUT4 protein to the plasma membrane and an increase in glucose transport activity. In our study, we evaluated the effect of chronic insulin treatment on the osmotic shock signaling pathway leading to GLUT4 translocation and glucose uptake. We found that chronic administration of insulin to the adipocytes induced cellular resistance to osmotic shock-stimulated GLUT4 translocation and glucose transport. We found that chronic insulin treatment attenuated shock-induced Gab-1 tyrosine phosphorylation. Furthermore, chronic insulin exposure led to a marked impairment in the ability of Gab-1 to associate with p85 subunit of PI 3-kinase in response to acute shock and insulin stimulation. Cells that were chronically treated with insulin showed a 70% and a 61% decrease in Gab-1 associated PI 3-kinase activity in shock- vs. insulin-treated cells, respectively. In addition, we found that chronic insulin treatment inhibited both insulin- and osmotic shock-induced membrane ruffling, indicating that two PI 3-kinase dependent effects, GLUT4 translocation and membrane ruffling are decreased in chronically insulin-treated cells. The results described above clearly demonstrate that chronic insulin treatment induces a state of cellular resistance to osmotic shock signal transduction.
Deskriptorji		INSULIN RESISTANCE INSULIN ADIPOCYTES MONOSACCHARIDE TRANSPORT PROTEINS OSMOTIC PRESSURE 3T3 CELLS ACTINS BIOLOGICAL TRANSPORT CELL MEMBRANE ENZYME ACTIVATION GLUCOSE MICE PHOSPHOPROTEINS PHOSPHORYLATION PHOSPHOTYROSINE SIGNAL TRANSDUCTION