Summary of Blood Glucose Regulation
In a normal person, the blood glucose concentration is narrowly
controlled, usually between 80 and 90 mg/ 100 ml of blood in the fasting person
each morning before breakfast. This concentration increases to 120 to 140
mg/100 ml during the first hour or so after a meal, but the feedback systems
for control of blood glucose return the glucose concentration rapidly back to
the control level, usually within 2 hours after the last absorption of
carbohydrates. Conversely, in starvation, the gluconeogenesis function of the
liver provides the glucose that is required to maintain the fasting blood glucose
The mechanisms for achieving this high degree of control have been
presented. Let us summarize them.
1. The liver functions as an important blood glucose buffer system. That is, when the blood
glucoserises to a high concentration after a meal and the rate of insulin
secretion also increases, as much as two thirds of the glucose absorbed from
the gut is almost immediately stored in the liver in the form of glycogen.
Then, during the succeeding hours, when both the blood glucose concentration
and the rate of insulin secretion fall, the liver releases the glucose back
into the blood. In this way, the liver decreases the fluctuations in blood
glucose concentration to about one third of what they would otherwise be. In
fact, in patients with severe liver disease, it becomes almost impossible to
maintain a narrow range of blood glucose concentration.
2. Both insulin and glucagon function as important feedback control
systems for maintaining a normal blood glucose concentration. When the
glucoseconcentration rises too high, insulin is secreted; the insulin in turn
causes the blood glucose concentration to decrease toward normal. Conversely, a
decrease in blood glucose stimulates glucagon secretion; the glucagon then
functions in the opposite direction to increase the glucose toward normal.
Under most normal conditions, the insulin feedback mechanism is much more
important than the glucagon mechanism, but in instances of starvation or
excessive utilization of glucose during exercise and other stressful situations,
the glucagon mechanism also becomes valuable.
3. Also, in severe hypoglycemia,
a direct effect of low blood glucose on the hypothalamus stimulates the
sympathetic nervous system. In turn, the epinephrine secreted by the adrenal
glands causes still further release of glucose from the liver. This, too, helps
protect against severe hypoglycemia.
4. And finally, over a period of
hours and days, both growth hormone and cortisol are secreted in response to
prolonged hypoglycemia, and they both decrease the rate of glucose utilization
by most cells of the body, converting instead to greater amounts of fat
utilization. This, too, helps return the blood glucose concentration toward
of Blood Glucose Regulation. One might ask thequestion:Why is it so
important to maintain a constant blood glucose concentration, particularly
because most tissues can shift to utilization of fats and proteins for energy
in the absence of glucose? The answer is that glucose is the only nutrient that
normally can be used by the brain,retina, and germinal epitheliumof the gonads in sufficient quantities to supply
themoptimally with their required energy. Therefore, it is important to
maintain the blood glucose concentration at a sufficiently high level to
provide this necessary nutrition.
Most of the glucose formed by gluconeogenesis during the
interdigestive period is used for metabolism in the brain. Indeed, it is
important that the pancreas not secrete any insulin during this time;
otherwise, the scant supplies of glucose that are available would all go into
the muscles and other peripheral tissues, leaving the brain without a nutritive
It is also important that the blood glucose concen-tration not rise
too high for four reasons: (1) Glucose can exert a large amount of osmotic
pressure in the extracellular fluid, and if the glucose concentration rises to
excessive values, this can cause considerable cellular dehydration.(2) An
excessively high level of blood glucose concentration causes loss of glucose in
the urine. (3) Loss of glucose in the urine also causes osmotic diuresis by the
kidneys, which can deplete the body of its fluids and electrolytes.(4)
Long-term increases in blood glucose may cause damage to many tissues,
especially to blood vessels. Vascular injury, associated with uncontrolled
diabetes mellitus, leads to increased risk for heart attack, stroke, end-stage
renal disease, and blindness.