NUTRITIONAL STATE REGULATES INSULIN-RECEPTOR AND IRS-1 PHOSPHORYLATION AND EXPRESSION IN CHICKEN

After insulin binding, insulin receptors (IR) phosphorylate the insuli n receptor substrate 1 (IRS-1) on specific motifs and thereby initiate insulin action. The interaction between IR and IRS-1 and their expres sion were studied in vivo in two target tissues (muscle and liver) in chickens, a species that is insulin resistant. To induce extreme chang es in plasma insulin levels, chickens were subjected to three differen t nutritional states (ad libitum fed, fasted for 48 h, and refed for 3 0 min after 48-h fast). Liver membrane IR number was significantly inc reased in fasted compared with fed chickens. This upregulation of IR n umber was concomitant with the an enhanced expression of IR mRNA as de termined by reverse transcription-polymerase chain reaction. In leg mu scle, IR mRNA. was not altered by the nutritional state. Using specifi c antibodies directed toward human IR, anti-phosphotyrosines, or mouse IRS-1, we demonstrated that IR and IRS-1 are associated in vivo in li ver and muscles. Tyrosine phosphorylation of liver IR and IRS-1 were s ignificantly decreased by prolonged fasting and restored by 30-min ref eeding. These alterations were not observed in muscle. Fasting increas ed IRS-1 mRNA expression in liver but not in muscle. These results are the first evidence showing that chicken liver and muscle express IRS- 1. Therefore, the chicken insulin resistance is not accounted for by t he lack of IRS-1. The differences observed for the regulation of IR an d IRS-1 messengers and phosphorylation between liver and muscle in res ponse to alterations of the nutritional state remain to be explained.