Insulin coordinates synthesis of proteins across multiple
compartments with proteostasis network.
A, gene ontology of newly made proteins
significantly increased in response to insulin are highlighted
in blue and depicted in the illustration of a
cell. TCA, tricarboxylic acid;
PPP, pentose phosphate pathway. Bar graphs
depict the percent increase in abundance of ER UPR,
mitochondrial (Mito) UPR, or cytosolic
chaperone proteins synthesized after 48-h incubation with
insulin compared with control. Black bars
indicate significantly insulin-regulated proteins. The
blue horizontal bar indicates the
interquartile range of the percent increase in insulin-regulated
proteins. B, 3T3-L1 adipocytes were treated
with insulin (Ins) for 24 h, and cell lysates
were immunoblotted for the indicated proteins.
Con, control. Immunoblots were quantified
and normalized to loading control and untreated samples
(n = 5 for phosphorylated IRE1
(pIRE1) and EIF2α
(pEIF2α); n = 3 for
phosphorylated PERK (pPERK); error
bars represent S.E.; one-sample t
test; *, p < 0.05). C and
D, rats were cannulated and infused with 40
mg/kg/min glucose for the indicated periods or saline
(Sal) for 4 days (d).
C, plasma glucose and insulin levels are
reproduced from Laybutt et al. (46). D,
adipose tissue of rats was immunoblotted for the indicated
proteins. Immunoblots were quantified and normalized to loading
control and saline samples (n = 4;
error bars represent S.E.; two-sample
t test; *, p < 0.05).
E, 3T3-L1 adipocytes were serum-starved for
1.5 h and treated with insulin for the indicated times. Cell
lysates were immunoblotted with the indicated antibodies.
Immunoblots were quantified and normalized to 14-3-3. Data were
scaled so that basal is set to 0, and the maximal response set
to 1 (n = 4; error bars
represent S.E.; one-sample t test; *,
p < 0.05). F and
G, 3T3-L1 adipocytes were serum-starved for
1.5 h and treated with the indicated inhibitors for 30 min
followed by insulin for 30 min. Cell lysates were immunoblotted
for the indicated proteins. Vertical lines on
the immunoblots indicate where the blot was spliced. Immunoblots
were quantified and normalized (norm) to
14-3-3. Insulin-stimulated phosphorylated IRE1 is expressed as
-fold change relative to DMSO-treated samples (indicated by the
dotted line) (F,
n = 4; G,
n = 5; error bars
represent S.E.; one-sample t test; *,
p < 0.05). Rap,
rapamycin; CHX, cycloheximide.