In part 1, part 2, and part 3
of this series, you learned how there are a lot of misconceptions on
how insulin works in the body, and how it has been unfairly blamed for
weight and fat gain in our society. In this article, I am going to
dismantle one of the biggest insulin myths of them all...a myth that has
been perpetuated in textbooks and is still taught in college
classrooms, despite the fact it was shown to be wrong over 25 years ago.
Insulin Is Not Required for Cells To Take Up Glucoseof this series, you learned how there are a lot of misconceptions on
how insulin works in the body, and how it has been unfairly blamed for
weight and fat gain in our society. In this article, I am going to
dismantle one of the biggest insulin myths of them all...a myth that has
been perpetuated in textbooks and is still taught in college
classrooms, despite the fact it was shown to be wrong over 25 years ago.
Are you surprised by the heading above? Many people think that your
cells need insulin to take sugar out of the blood. One of the pieces of
evidence that is offered for this is the type I diabetic. When a type I
diabetic has no insulin, blood sugar skyrockets. This is supposedly
because sugar can't get into cells.
However, the above scenario is not what happens in a type I diabetic
that has been taken off of insulin. Sugar can get into the cells just
fine. There's actually something else going on. A review paper published in the Journal of Anasthesia
thoroughly describes how insulin has been misunderstood in its role in
blood sugar regulation, and I will summarize this paper here, along with
some of my own comments.
A Man Ahead of His Time
In 1916, Sir Edward Schafer, a professor of physiology, published a book called The Endocrine Organs. In this book, he hypothesized the existence of what we now call insulin:
The results of pancreas extirpation and pancreasInsulin would go onto be discovered 8 years later. Schafer also
grafting are best explained by supposing that the islet tissue produce
an Autacoid which passes into the blood stream and effects carbohydrate
metabolism and carbohydrate storage in such a manner that there is no
undue accumulation of glucose in the blood. Provisionally it will be
convenient to refer to this hypothetical substance as insuline.
hypothesized that insulin was created from an inactive precursor:
It must however be stated that it has yet to bePro-insulin was discovered nearly 50 years later. Schafer was truly a man ahead of his time.
determined whether the active substance is produced as such in the
pancreas or whether it exists there as pro-insuline which becomes
elsewhere converted into an active autacoid.
Schafer avoided using the term "hormone" to describe insulin.
Instead, he used the terms "autacoid" and "chalone." An autacoid was a
substance with excitatory action, meaning it stimulated things to happen
in your body. An autacoid can be thought of as similar to the gas
pedal in your car; you step on the pedal and it stimulates your car to
go faster. A chalone was a substance with inhibitory action; it slows
things down in your body. A chalone can be thought of as similar to the
brake in your car. Schafer correctly hypothesized that insulin acted
as both an autacoid and chalone in your body. He also considered that
insulin acted as much more of a chalone than an autacoid in your body.
In other words, he felt that insulin's inhibitory functions were much
more important than its excitatory or stimulatory functions. He would
be proven correct many years later.
The Black Age of Endocrinology
However, before Schafer was proven correct, the "Black Age of
Endocrinology" ensued. This was the time period between 1950 and 1980,
where scientists extrapolated beyond their discoveries. They took in vitro animal data (research performed in a test tube or culture), and then assumed that the same thing happens in humans in vivo (inside the body). In fact, one of the reasons I am so highly critical of Gary Taubes and his Good Calories, Bad Calories book
is that he relies heavily on research from this period, despite the
fact that much of what was thought then has either been overturned by
better research, or at least significantly altered. Taubes even stated
around the 31 minute mark in this interview
that he doesn't pay attention to modern research because "all of this
should have been obvious decades ago." This is a surprising stance for a
science writer; I would think that he would understand that conclusions in science are always tentative.
This is particularly true in the nutritional and physiological
sciences, where advances in measurement techniques have allowed us to
measure and discover things that we could not measure before; this has
overturned or modified many hypotheses and thoughts over the years. But
I digress.
The Black Age of Endocrinology is what led to the now mistaken belief
that insulin is needed for your cells to take up glucose. Experiments
in the 1950s showed that insulin could stimulate bits of rat muscle and
fat to take up glucose. This data was extrapolated to humans, and it
was then incorrectly hypothesized that a lack of insulin results in
glucose not being able to get inside your cells, and thus blood glucose
climbs to dangerous levels. This erroneous thinking has now been taught
in textbooks and college classes all over the world for many years,
resulting in dogma. Unfortunately, it is very difficult to overcome
dogma, and even though this concept of insulin was shown to be wrong in
the 1970's, it still continues to be taught to this day.
Glucose Transport is Not Insulin Dependent
The erroneous hypothesis that insulin withdrawal results in high
blood glucose because "glucose can't get into cells" was based on the
assumption that insulin is required for cells to take up glucose, rather than insulin merely enhancing
glucose uptake. What the scientists in the 1950s failed to note was
how tissues can take up considerable amounts of glucose even when
insulin is absent.
Glucose enters your cells via a family of transporters. A primary
transporter in muscle and fat cells is known as GLUT-4. Insulin
stimulates GLUT-4 to move from the interior of a cell to the cell
surface, where the glucose can then bind to the GLUT-4 transporter and
enter the cell. However, there are plenty of glucose transporters on
the cell surface, even when there is no insulin. In fact, there are
enough transporters on the cell surface to allow the cell to get enough
glucose to sustain its energy needs. Thus, glucose transport into cells
is never truly dependent upon insulin. Insulin enhances the uptake of
glucose into cells, but it is not required for it. In fact, when you
knock out the insulin receptor in mice so that insulin cannot stimulate
glucose uptake into muscle or fat cells (yet you keep the insulin
receptor intact on other cells like brain and liver), the animals do not become diabetic and they have normal blood sugars.
What Really Happens in a Type I Diabetic
Metabolic tracer studies have allowed us to learn how insulin operates in humans in vivo.
When you take a type I diabetic off insulin, blood glucose climbs
sharply. However, it's not because glucose can't get into cells. In
fact, glucose uptake into cells actually increases. This is because the
concentration of glucose in the blood is so much higher than the
cellular concentration that glucose must move into the cells (remember,
there's already enough glucose transporters on the cell surface even if
there's no insulin). So why does blood glucose climb so high? Remember
that the amount of glucose in your blood is both a function of how much
glucose is entering the blood (the rate of appearance), as well as how much glucose is leaving the blood (the rate of disappearance).
In a fasted diabetic without insulin, all of the glucose is coming from
the liver. Remember that your liver helps maintain blood sugar levels
when you are fasted by releasing glucose; this glucose comes from both gluconeogenesis (the formation of glucose from non-carbohydrate sources, like protein) and glycogenolysis
(the breakdown of glycogen stored in your liver). Insulin acts as a
brake (a chalone as Dr. Schafer described it) on these processes. Thus,
when you do not have insulin, you have runaway gluconeogenesis and
glycogenolysis. The high blood sugar in an uncontrolled diabetic is
thus caused by overproduction of glucose from the liver, not because
glucose can't get into cells.
In fact, since insulin is not present, many processes go forth at
high rates, completely unregulated. Insulin normally inhibits the
production of ketones by your liver; without insulin to slow down ketone
production, ketones are produced at high rates, resulting in diabetic
ketoacidosis. This is why hyperglycemia and ketoacidosis occur
simultaneously. Without insulin, you also have accelerated proteolysis
(the breakdown of protein) and lipolysis (the breakdown of fat). The
elevated amino acids in the blood provide further substrate for the
liver to continue to produce large amounts of glucose. The elevated
fatty acids provide substrate for the liver to continue to produce large
amounts of ketones.
Thus, insulin is like a traffic cop or a stop light at an
intersection. It helps slow down and control traffic. Without a stop
light or traffic cop, cars go through the intersection uncontrolled and
you get traffic accidents. Likewise, without insulin in the body,
gluconeogenesis, glycolysis, proteolysis, ketogenesis, and lipolysis all
proceed at high rates without anything to stop them. The end result is
hyperglycemia, ketoacidosis, and eventually death.
When you inject insulin into an uncontrolled diabetic, you are now
providing a brake on all of the processes mentioned earlier. You
inhibit production of glucose by the liver, so blood sugar falls.
Because there is no longer hyperglycemia, glucose uptake into cells
actually decreases. Lipolysis is inhibited, so free fatty acid
concentration falls to near zero. Because there are no longer free
fatty acids to make ketones, ketone production slows down. Proteolysis
is also inhibited.
Insulin...More of a Traffic Cop Than a Storage Hormone
Metabolic tracer studies have proven what Schafer had hypothesized
nearly a century ago...that insulin's main role in the body is
inhibitory rather than excitatory. While insulin certainly does have
excitatory functions, it is not primarily a "storage hormone" that many
individuals claim that it is. Insulin is not needed for your cells to
take up and store glucose. Certainly, it enhances uptake, but there is a
big difference between enhancing uptake and being needed for uptake.
Of course, this research only tells us what happens when insulin
is present versus when it is not present. What about the normal
situation of a healthy person, who ingests a meal and sees a rise in
blood glucose? What is happening to bring glucose back to normal? And
what happens in a type II diabetic in this situation? Learn the answers to these questions by reading part 6 of the series. Also click here to read part 5 where I address comments made by some of the critics of this series.
REFERENCE: Sonksen, P., and Sonksen, J. Insulin: understanding its action in health and disease. British Journal of Anaesthesia. 85(1):69-79, 2000.
