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