cron-web.org

[A1CR]

http://en.wikipedia.org/wiki/Adiponectin appears to play a
role in how CR
affects blood sugar utilization.

Zhu M, Miura J, Lu LX, Bernier M, DeCabo R, Lane MA, Roth
GS, Ingram DK.
Circulating adiponectin levels increase in rats on caloric
restriction: the
potential for insulin sensitization.

Exp Gerontol. 2004 Jul;39(7):1049-59.

PMID: 15236764

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15236764

Abstract:

Caloric restriction (CR) ... we show a significant
increase in plasma
adiponectin and a decrease in blood glucose, plasma
triglyceride and insulin
levels in rats maintained on CR diet for 2, 10, 15, and 20
months. Long-term
CR rats exhibited significantly higher insulin-stimulated
insulin receptor
tyrosine phosphorylation and lower PTP-1B activity both in
liver and
skeletal muscle than those observed in rats fed ad libitum
(AL). In
addition, the triglyceride levels in these tissues were
significantly lower
in long-term CR animals. Interestingly, concentrations of
plasma adiponectin
in long-term CR rats were associated with increased
expression of the
transcription factor mRNAs for the peroxisome
proliferator-activated
receptor (PPAR)alpha, gamma and delta, but decreased
expression for
SREBP-1c, resulting in a concerted modulation in the
expression of key
transcription target genes involved in fatty acid oxidation
and energy
combustion in liver. Taken together, our findings suggest an
important role
for adiponectin in the beneficial effects of long-term CR.

Excerpts:

... white adipose tissue plays a vital role in
regulating energy and
glucose homeostasis ... in part by producing a number of
biologically active
proteins. Proteins secreted by adipose tissue, now referred
to as adipokines
or adipocytokines ... Unlike many of the other adipokines,
the expression of
adiponectin mRNA and circulating levels of its product are
significantly
reduced in diabetic and obese conditions in mice ...
Reduction in the plasma
adiponectin ... contributing to insulin resistance and the
development of
type 2 diabetes ... adiponectin improved insulin sensitivity
while lowering
blood glucose ... In female CR nondiabetic mice, the plasma
adiponectin
levels are 2- to 3-fold higher ...

Male Fischer-344 rats ... weaned at 28 days ... CR,
provided with a
daily food allotment of 60% of that eaten by the AL rats,
supplied with
NIH-31 mineral and vitamin supplemented rodent chow ...


... We examined changes in body weight and various
blood and plasma
parameters in fasted rats as a function of age and diet (AL
vs. CR). There
were significant age and/or diet effects, as well as
significant age by diet
interactions for body weight, blood glucose, and plasma
insulin, adiponectin
and triglyceride concentrations. These results are
summarized in Table 2.
Regarding body weight, AL rats significantly gained weight
from 2 months of
age, while the CR rats did not and were significantly
lighter than AL
counterparts at each age. Blood glucose was relatively
constant across age
among AL rats but actually decreased with age in the CR
group. Except at 2
months of age where blood glucose levels were actually
higher among CR rats
compared to AL, glucose was significantly lower in the CR
group at all other
ages. Plasma insulin increased with age compared to the
2-month group in
both the AL and CR groups, but insulin levels were
significantly lower in
the CR group at every age. Major CR effects were also
observed in plasma
adiponectin levels. At every age, levels were 2- to 3-fold
higher in CR rats
compared to AL. In the AL group, adiponectin levels remained
about the same
across age but compared to the level recorded for 2 months
old rats, levels
were clearly higher in the CR group at all older ages.
Plasma glucagon
levels also remained constant across age in the AL group,
while in the CR
group the highest level was recorded in the oldest group;
however, we saw no
significant CR effects on glucagon at any age. Plasma
triglyceride levels
were significantly reduced in rats maintained on 10, 15, and
20 months CR
diet.

[...]
... Effect of CR on levels of insulin receptor (IR)
tyrosine
phosphorylation (pY) in liver, skeletal muscle and pancreas

... maintained on either CR or AL diet for 2 and 25
months. In these
tissues, basal pY-IR levels did not differ significantly
between diet groups
at either 2 or 25 months (data not shown). However, after a
single portal
vein injection of insulin, pY-IR was significantly increased
in the liver
(p=0.06) and muscle (p=0.003) of rats maintained on the
25-month CR diet
compared with age-matched AL controls (n=5-6) (Fig. 1). Note
that in rats
maintained on AL diet, there was a significant age-dependent
reduction in
insulin-induced pY-IR in liver and muscle, but not in
pancreas (Fig. 1). The
pY-IR levels were indistinguishable in all tissues tested
for the rats
maintained on both AL and CR diets for 2 months. In the
25-month group,
however, pY-IR was significantly higher in both CR liver
(51%) and skeletal
muscle (58%) relative to the age-matched AL controls. pY-IR
in CR pancreas
tended to increase (13%), but this diet-related increase did
not achieve
statistical significance (p=0.17). These results indicated
that CR
attenuated the age-related decline in insulin-stimulated
pY-IR only in
insulin sensitive tissues.

[...]

... Effect of CR on PTP-1B activity in liver, skeletal
muscle and
pancreas

.[...]

... Triglyceride (TG) content in liver, skeletal
muscle and pancreas
We then explored the possibility that the improved insulin
receptor
signaling in CR rats was a consequence of higher plasma
adiponectin levels
(Table 2) with concomitant reduction in TG content in
tissues. In the AL
group, there was an age-dependent increase in TG content in
liver (p=0.04)
and muscle (p=0.07), but not in pancreas (Fig. 3). In
contrast, rats
maintained on CR diet exhibited no increase in TG content in
all tissues
tested as a function of age. Interestingly, rats maintained
on the 25-month
CR diet exhibited a 43 and 41% reduction in TG content in
liver and muscle,
respectively, compared to age-matched AL controls (Fig. 3).
However, TG
content was not significantly different in all tissues
tested for rats
maintained on both diets for 2 and 13 months. [Agsain,
values were less for
CR at all time points in all three organs.]

... Effects of CR on mRNA levels for the transcription
factors and
genes involved in lipid metabolism


[...]

... Like in CR rats, mice harboring an
adipose-specific insulin
receptor knockout (FIRKO) have a marked reduction in fat
mass and whole body
triglyceride stores, but exhibit high plasma adiponectin
concentration [http://tinyurl.com/l8swq paper]. ... FIRKO
mice were found to
have an increase in median and maximum lifespan [the
pdf-availed
http://tinyurl.com/me5ph paper]. ... the present study ...
CR enhanced
circulating adiponectin and decreased plasma triglyceride
levels, resulting
in reduced triglyceride accumulation in tissues, thereby
improving insulin
receptor signaling. ...