S. Marandi et al., Insulin signal transduction in rat small intestine: role of MAP kinases inexpression of mucosal hydrolases, AM J P-GAST, 280(2), 2001, pp. G229-G240
Citations number
57
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
The postreceptor events regulating the signal of insulin downstream in rat
intestinal cells have not yet been analyzed. Our objectives were to identif
y the nature of receptor substrates and phosphorylated proteins involved in
the signaling of insulin and to investigate the mechanism(s) by which insu
lin enhances intestinal hydrolases. In response to insulin, the following p
roteins were rapidly phosphorylated on tyrosine residues: 1) insulin recept
or substrates-1 (IRS-1), -2, and -4; 2) phospholipase C-isoenzyme-gamma; 3)
the Ras-GTPase-activating protein (GAP) associated with Rho GAP and p62(Sr
c); 4) the insulin receptor beta -subunit; 5) the p85 subunits of phosphati
dylinositol 3-kinase (PI 3-kinase); 6) the Src homology 2 alpha -collagen p
rotein; 7) protein kinase B; 8) mitogen-activated protein (MAP) kinase-1 an
d -2; and 9) growth receptor-bound protein-2. Compared with controls, insul
in enhanced the intestinal activity of MAP kinase-2 and protein kinase B by
two- and fivefold, respectively, but did not enhance p70/S6 ribosomal kina
se. Administration of an antireceptor antibody or MAP-kinase inhibitor PD-9
8059 but not a PI 3-kinase inhibitor (wortmannin) to sucklings inhibited th
e effects of insulin on mucosal mass and enzyme expression. We conclude tha
t normal rat enterocytes express all of the receptor substrates and mediato
rs involved in different insulin signaling pathways and that receptor bindi
ng initiates a signal enhancing brush-border membrane hydrolase, which appe
ars to be regulated by the cascade of MAP kinases but not by PI 3-kinase.