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Fig. 14.4
Protein expression of (
a
) p-PERK and (
b
) BIP in liver of NP, NPT, LP, and LPT mice.
Values are mean ± SEM (
n
= 5); different letters over bars indicate statistical difference;
P
< 0.05
(two-way ANOVA, Newman-Keuls post hoc test)
months of age insulin signaling in adipocytes was impaired (Ozanne et al.
2001
) and
at 17 months, these rats become diabetic (Petry et al.
2001
). Since ER stress impairs
insulin signaling and is associated to the pathogenesis of obesity and type 2 diabetes
(Ozcan et al.
2004
; Zhou et al.
2011
), we believe that this pathway may link the
transition from increased sensitivity to insulin resistance that occurs throughout the
life span in malnourished rodents.
Finally, we observed that TAU supplementation normalized ER stress markers in
the liver from malnourished mice and lowered their expression in pancreatic islets
from both supplemented groups (Figs.
14.3
and
14.4
). TAU was reported to reduce
ER stress induced by several agents in different tissues and cell types. In primary
neuron cultures, TAU treatment reduces hypoxia and glutamate-induced ER stress
(Pan et al.
2012
). TAU protects H4IIE liver cells from palmitate-induced cell death
and caspase-3 activation and prevents hepatic steatosis in high sucrose-fed rats
through suppression of the PERK/eIF2/ATF4 branch of the ER stress pathway
(Gentile et al.
2011
). The proper mechanisms by which TAU reduces ER stress are
still not clear. Here we show for the first time that TAU supplementation increases
p-Akt in pancreatic islets and acute incubation with this amino acid increased islet
p-ERK1/2 content (Fig.
14.3e, f
). These findings could be explained by a direct
interaction of TAU with the insulin receptor leading to its activation (Maturo &
Kulakowski
1988
; Carneiro et al.
2009
). Transgenic mice overexpressing Akt in the
heart showed prevention of contractile dysfunction provoked by tunicamycin, a
chemical that induces ER stress (Zhang et al.
2011
). Thus, TAU-induced increase in
Akt activation (Fig.
14.3e
) could contribute to decreased ER stress protein expres-
sion in pancreatic islets.
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