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VOL. 76 (1), 23-44, 2010 BETA-CELL HYPERPLASIA INDUCED BY HEPATIC INSULIN...

3.2. Progressive insulin resistance and glucose intolerance
3.2. in inducible LIRKO

At 6 months of age iLIRKO mice demonstrated defects in insulin
signaling proportional to the lost of IR expression. Thus, in the group
with 50% of IR expression, there was a marked decreased in Akt,
ERKs and p70-S6-kinase activation while in the group with complete
IR deletion; there was a virtual absence of insulin activation of these
enzymes. Interestingly, despite the fact that there was no IR lost in
other tissues (Figure 1, panel B), there was a progressive impairment
of insulin signaling in other peripheral tissues. Thus, there was
progressive insulin impairment on Akt, ERKs and p70-S6-kinase
signaling from 50 to 0% IR expression left by the liver, in brain,

Figure 2. Liver Histology and Metabolic Gene Expression in iLIRKO mice.
A) Periodic Acid-Schiff reagent (PAS), Hematoxylin/Eosin and Masson staining of
liver sections from random-fed, 6-month- and 1-year-old male control (upper panel)
and iLIRKO (lower panel) mice. A representative experiment out of four is shown.
Magnification 20X. B) Protein liver extracts from 6-month-old Wt, IR(loxP/loxP) and
iLIRKO mice were analyzed by Western blot. A representative experiment out of
five is shown. Histograms show the densitometric analysis.

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