The nutritional state regulates insulin receptor and insulin receptor substrate 1 phosphorylation and expression in chicken. Dupont, Jolle, Michel Derouet, Jean Simon, and Mohammed Taouis. Endocrinologie de la Croissance et du M[theta]tabolisme, Station de Recherches Avicoles, INRA, 37380 Nouzilly, France.
APStracts 4:0238E, 1997.
Upon insulin binding, insulin receptors (IR) phosphorylate the insulin receptor substrate 1 (IRS-1) on specific motifs and thereby initiate insulin action. The interaction between IR and IRS-1 and their expression was studied in vivo in two target tissues (muscle and liver) in chickens, a species which is insulin resistant. In order to induce extreme changes in plasma insulin levels, chickens were subjected to three different nutritional states (ad libitum fed, fasted for 48 hours and refed for 30 min after 48 hours of fast). Liver membrane insulin receptor number was significantly increased in fasted compared to fed chickens. This up-regulation of insulin receptor number was concomitant with the an enhanced expression of IR mRNA as determined by RT-PCR. In leg muscle, IR mRNA was not altered by the nutritional state. By using specific antibodies directed toward human IR, antiphosphotyrosines or mouse IRS-1, we demonstrated that IR and IRS-1 are associated in vivo in liver and muscles. Tyrosine phosphorylation of liver IR and IRS-1 were significantly decreased by prolonged fasting and restored by 30 min refeeding. These alterations were not observed in muscle. Fasting increased 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 the lack of IRS-1. The differences observed for the regulations of IR and IRS-1 messengers and phosphorylation between liver and muscle, in response to alterations of the nutritional state remain to be explained.

Received 9 June 1997; accepted in final form 24 October 1997.
APS Manuscript Number E264-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 14 November 1997