Disruption of body clock linked to diabetes, obesity and heart
24 February 2013
For the first time a study has shown that insulin production
follows the body’s circadian rhythm and disruption of this can
increase the risk of obesity, diabetes and heart disease.
The study, conducted by a team from Vanderbilt University and
published in the journal Current Biology (21 Feb 2013),
is the first to show definitively that insulin activity is
controlled by the body’s circadian biological clock, and helps
explain why it is not only what you eat, but when you eat, that
In recent years, a number of studies in both mice and men have
found a variety of links between the operation of the body’s
biological clock and various aspects of its metabolism, the physical
and chemical processes that provide energy and produce, maintain and
destroy tissue. It was generally assumed that these variations were
caused in response to insulin, which is one of the most potent
metabolic hormones. However, no one had actually determined that
insulin action follows a 24-hour cycle or what happens when the
body’s circadian clock is disrupted.
Because they are nocturnal, mice have a circadian rhythm that is
the mirror image of that of humans: They are active during the night
and sleep during the day. Otherwise, scientists have found that the
internal timekeeping system of the two species operate in nearly the
same way at the molecular level. Most types of cells contain their
own molecular clocks, all of which are controlled by a master
circadian clock in the suprachiasmatic nucleus in the brain.
Insulin, which is made in the pancreas, plays a key role in
regulating the body’s fat and carbohydrate metabolism. When we eat,
digestion breaks down the carbohydrates in our food into the simple
sugar glucose, which is absorbed into the blood stream. Too much
glucose in the blood is toxic, so one of insulin’s roles is to
stimulate transfer of glucose into our cells, thereby removing
excess glucose from the blood. Specifically, insulin is required to
move glucose into liver, muscle and fat cells. It also blocks the
process of burning fat for energy.
Insulin action — the hormone’s ability to remove glucose from the
blood — can be reduced by a number of factors and is termed insulin
resistance. The study found that normal "wild-type" mouse tissues
are relatively resistant to insulin during the inactive/fasting
phase whereas they become more sensitive to insulin (therefore
better able to transfer glucose out of the blood) during the high
activity/feeding phase of their 24-hour cycle. As a result, glucose
is converted primarily into fat during the inactive phase and used
for energy and to other tissue building during the high activity
“That is why it is good to fast every day — not eat anything
between dinner and breakfast,” said Johnson.
The researchers also examined what happened to insulin action
when the circadian clocks of individual mice are disrupted.
One approach used was to study special “knock-out” mice that had
one of the genes necessary for proper biological clock function
removed. They found these mice appeared to be locked in an
insulin-resistant mode around the clock comparable to the
inactive/fasting phase. After feeding on a high-fat diet, they
tended to gain more weight and carry more fat than wild-type mice.
However, supplying them with the protein produced by the missing
gene re-established their circadian rhythm, reduced their insulin
resistance and prevented them from gaining excess fat.
Another approach was to place normal "wild-type" mice in a
constantly lit environment that disrupted their circadian cycle. In
this case, they found the mice were locked in the inactive/fasting
phase, developed a higher proportion of body fat and gained more
weight on a high-fat diet than wild-type mice despite actually
eating less food. Obesity and the insulin resistance that
accompanies it, increases the risk of diabetes and cardiovascular
According to the researchers, this helps explain the increased
frequency of obesity and diabetes among night-shift workers and
people suffering from disruption of their clocks and normal sleep
The researchers also found that high-fat diets disrupted the
circadian clock of wild-type mice living in a normal day/night
cycle. As a result, their insulin cycle defaulted to the
inactive/fasting phase, which helps explain why high-fat diets lead
to weight gain.