Regulation of insulin-stimulated tyrosine phosphorylation of Shc and Shc/Grb2 association in liver, muscle, and adipose tissue of epinephrine- and streptozotocin-treated rats
V. Paez-espinosa et al., Regulation of insulin-stimulated tyrosine phosphorylation of Shc and Shc/Grb2 association in liver, muscle, and adipose tissue of epinephrine- and streptozotocin-treated rats, ENDOCRINE, 14(3), 2001, pp. 295-302
Shc protein phosphorylation has been extensively characterized as the initi
al step that activates a complex mitogenic pathway through its association
with Grh2. In the present study, we investigated the adrenergic control of
insulin-induced She phosphorylation and Shc-Grb2 association, and the modul
ating effect of streptozotocin-induced diabetes mellitus on She phosphoryla
tion and Shc/Grb2 association. Acute treatment with epinephrine, which lead
s to a normoglycemic insulin-resistant state, does not affect insulin-induc
ed She tyrosine phosphorylation or Shc-Grb2 association in liver, muscle, o
r fat. By contrast, a significant increase in insulin-induced She phosphory
lation is observed in liver and muscle of rats treated with streptozotocin.
The association of Shc/Grb2 is also increased in both tissues following in
sulin treatment, These data suggest that while epinephrine preserves the in
sulin/induced phosphorylation of She and the mitogenic pathway stimulated b
y Shc-Grb2 association, treatment with streptozotocin leads to a tissue-spe
cific increase in the activity of the initial step that ultimately results
in the activation of the Shc/Grb2 mitogenic pathway.