"Insulin is important in the regulation of blood sugar, but its
importance has been exaggerated because of the diabetes/insulin industry.
Insulin itself has been found to account for only about 8% of the
"insulin-like activity" of the blood, with potassium being probably
the largest factor. There probably isn't any process in the body that doesn't
potentially affect blood sugar.
When I initially read this quotation posted by one of
Dr. Peat’s ardent followers on Facebook, it caught my attention because I was
under the impression that insulin was the dominant factor in regulating blood
glucose levels.
Normally, when blood levels increase, the beta-cells
of the pancreatic islets secrete insulin into the bloodstream, where it binds
to insulin receptors on organs and tissues throughout the body. The
adipose tissue, liver, and muscles are the principle sites that insulin exerts
its actions on. In effect, insulin is a storage hormone that rapidly
clears nutrients out of the bloodstream.
(1) In the fat tissue, insulin suppresses the
mobilization of fatty acids and promotes the synthesis of fatty acids and
triglycerides.
(2) In the liver, insulin inhibits
gluconeogenesis and glycogen breakdown and stimulates glucose oxidation and
glycogen synthesis.
(3) In the muscles, insulin stimulates amino acid
uptake and protein synthesis.
According to some of the most widely read physiology
textbooks, in the absence of insulin all of the above processes become
impaired, and fatty acids and amino acids are released in large amounts into
the bloodstream from the fat tissue and muscles, respectively. In the
liver, these fatty acids are used to generate ketone bodies and the amino
acids, substrates for gluconeogenesis, are used to generate glucose.
Because fatty acids flow to the liver at a high rate, and
because insulin normally stimulates the use of ketone bodies by cells in
the body, ketone bodies—namely acetone—accumulate in the bloodstream, thereby leading
to acidosis, coma, and death.
I think most people are also aware of experiments in
isolated segments of animal tissue, in which blood glucose levels are
incrementally increased in the absence of insulin (ex vivo). In
these experiments, despite increasing blood glucose levels by up to 800 mg/dL,
which is 10-fold greater than the normal fasting blood glucose levels, the
levels of glucose inside cells do not change much at all. What this means
is that, without insulin, regardless of how high blood glucose levels rise, the
entry of glucose into cells is prevented, and this is, for all intents and
purposes caused by a rise in NEFA and ketone body levels.
More recently, based on better, and more physiological,
experiments, it has been suggested that there could be constitutively active
glucose transporters; that is, proteins embedded in the plasma membrane that,
in an insulin-independent manner, transport glucose into cells.1 These transport proteins
are regulated by the unequal distribution of free glucose molecules between the
blood and inside the cell (i.e., the concentration gradient across the plasma
membrane), and the efficiency with which the glycolytic enzymes function.
So it is possible that insulin assumes a secondary, or
conditional, role in the regulation of blood glucose levels under some circumstances.
In the fasting state, when blood glucose levels fall, glucose is transported
into cells with, at the most, very little help from insulin . . . this process
being only limited by the rate at which the glycolytic enzymes
function.
But when blood glucose levels rise, as in after a
carbohydrate-laden meal, the beta-cells begin to secrete insulin, and insulin (1)
suppresses the mobilization of fatty acids, (2) suppresses hepatic glucose
production, and (3) stimulates the recruitment of glucose transport proteins to
the plasma membrane, whereby insulin-sensitive cells sprout orders of magnitude
more glucose transport proteins. In this way, glucose is cleared as
rapidly as it rises in the blood, because of insulin’s permissive effects, such
that blood glucose levels don’t fall out of range too much.
So, although insulin may not be the be-all and end-all
regulator of the rate at which glucose is transported into cells, it is by no
means a minor player as asserted by Dr. Peat. (Actually insulin is a protective
compensatory adaptation to the rising levels of the counterregulatory hormones
that occurs naturally with aging.)
As to potassium, it is known that inappropriately dosed
insulin injections can uncomfortably lower blood potassium levels (hypokalemia),
as insulin shifts potassium into cells.
By neutralizing ROS, potassium has also been
hypothesized to improve insulin sensitivity.2 Though, this is not having
'insulin-like action.' (As an aside, to date, the use of antioxidants to treat
diabetes has been abysmally unsuccessful.)
But then again, high potassium levels (hyperkalemia), in
turn, stimulates the secretion of aldosterone, which could worsen insulin
sensitivity.3 This is the same
mechanism by which salt-restricted diets induce insulin resistance.4
Potassium has another important role in blood glucose
regulation in the beta-cells. Without going into too much detail, when
blood glucose levels rise, the beta-cells uptake glucose,
which is then oxidized to generate ATP. This newly generated ATP,
thereafter, binds the ATP-sensitive potassium channels in the plasma membrane
that close upon this interaction with ATP, enabling potassium to accumulate
intracellularly. As a result, the membrane depolarizes, stimulating the
opening of the voltage-gated calcium channels that then allow calcium to move
into the beta-cell in droves, triggering insulin secretion.
It is conceivable that a deficiency of potassium could
impair insulin’s action (e.g., diuretics that deplete potassium have been shown
to induce insulin resistance). But as far as potassium having
insulin-like action, I don’t see any evidence for this.
Insulin’s actions are blocked by elevated levels of NEFA
and the counterregulatory hormones, in which case, the resulting inhibition of
the glycolytic enzymes would block the procession of glycolysis, leading to the
accumulation of free glucose molecules that could move out into the
extracellular space. This plays an important regulatory role while
fasting (a period of time when glucose availability is limited) and while under
stress, by preventing glucose from being used up too quickly . . . otherwise,
shock would manifest.
Insulin can be conceived to boost, in a permissive
manner, the clearance of glucose from the blood so that after eating a
carbohydrate-laden meal, per the mechanisms described above, blood glucose levels
don’t fall out of range too much or for too long. Gastrointestinal
hormones play a role in blood glucose regulation as well, but they do so by
potentiating the stimulation of insulin secretion from the pancreatic
beta-cells.
In conclusion, insulin occupies a major role in blood
glucose regulation—not a minor one. A rise in glucose is always quickly
accompanied by a rise in insulin in the bloodstream, and insulin suppresses the
factors that inhibit the rapid clearance and oxidation of glucose, which are
processes that would occur too inefficiently otherwise (that is, if glucose
were to stimulate its own uptake and oxidation). A situation like this
would only occur during a fast or ketogenic diet, cases in which fasting
glucose levels would run parallel with low insulin levels, prompting a slow and
controlled rate of glucose use. This is the scenario that Dr. Peat is
probably alluding to.
References
1. Sonksen PH. Insulin, growth hormone and sport. The Journal of endocrinology. 2001;170(1):13–25. Available at: http://www.ncbi.nlm.nih.gov/pubmed/11431133. Accessed February 14, 2013.
2. Ando K, Matsui H, Fujita M, Fujita T. Protective effect of dietary potassium against cardiovascular damage in salt-sensitive hypertension: possible role of its antioxidant action. Current vascular pharmacology. 2010;8(1):59–63. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19485915. Accessed February 14, 2013.
3. Kraus D, Jäger J, Meier B, Fasshauer M, Klein J. Aldosterone inhibits uncoupling protein-1, induces insulin resistance, and stimulates proinflammatory adipokines in adipocytes. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. 2005;37(7):455–9. doi:10.1055/s-2005-870240.
4. Garg R, Williams GH, Hurwitz S, Brown NJ, Hopkins PN, Adler GK. Low-salt diet increases insulin resistance in healthy subjects. Metabolism: clinical and experimental. 2011;60(7):965–8. doi:10.1016/j.metabol.2010.09.005.
