Human Physiology, 14th edition (2016)

678 Chapter 19

During the postabsorptive (fasting) state, the plasma glu-

cose concentration falls. As a result, insulin secretion decreases

and glucagon secretion increases (chapter 11; see fig. 11.31).

These changes in hormone secretion prevent the cellular

uptake of blood glucose into organs such as the muscles, liver,

and adipose tissue. An elevated glucagon secretion, in the pres-

ence of low insulin levels, also stimulates glycogenolysis and

so promotes the release of glucose from the liver. A negative

feedback loop is therefore completed, helping to retard the fall

in plasma glucose concentration that occurs during fasting.

The oral glucose tolerance test (see fig. 19.12 ) is a mea-

sure of the ability of the beta cells to secrete insulin and of the

ability of insulin to lower blood glucose. In this procedure, a

person drinks a glucose solution and blood samples are taken

periodically for plasma glucose measurements. In a normal

person, the rise in blood glucose produced by drinking this

(the postabsorptive state ). As a result, the secretion of insulin and
glucagon changes during these conditions and helps maintain
homeostasis of the plasma glucose concentration (chapter 11;
see fig. 11.31).
The targets of insulin action are primarily the cells of skel-
etal and cardiac muscles, adipose tissue, and the liver. In these
cells, intracellular vesicles containing GLUT4 carrier proteins
for glucose are stimulated by insulin to fuse with the plasma
membrane so that the GLUT4 carriers are at the cell surface
(chapter 11; see fig. 11.30). This permits the entry of glucose
into its target cells by facilitated diffusion. As a result, insulin
promotes the production of the energy-storage molecules of gly-
cogen and fat. Both actions decrease the plasma glucose concen-
tration. Insulin also inhibits the breakdown of fat, induces the
production of fat-forming enzymes, and inhibits the breakdown
of muscle proteins. Thus, insulin promotes anabolism as it regu-
lates the blood glucose concentration.
The mechanisms that regulate insulin and glucagon secretion
and the actions of these hormones normally prevent the plasma
glucose concentration from rising above 170 mg per 100 ml
after a meal or from falling below about 50 mg per 100 ml
between meals. This regulation is important because abnormally
high blood glucose can damage certain tissues (as may occur in
diabetes mellitus), and abnormally low blood glucose can dam-
age the brain. This can occur because glucose enters neurons by
facilitated diffusion driven by the higher glucose concentration
in the plasma. When low plasma glucose concentrations reduce
this diffusion gradient, the brain may not get sufficient glucose
for its metabolic needs. This can result in weakness, dizziness,
personality changes, and ultimately in coma and death.

Effects of Glucose and Amino Acids

The fasting plasma glucose concentration is in the range of
65 to 105 mg/dl. During the absorption of a meal, the plasma
glucose concentration usually rises to a level between 140 and
150 mg/dl. When plasma glucose levels are low, specific ATP-
gated K^1 channels in the beta cell plasma membrane are open.
This allows the efflux of K^1 and keeps the membrane hyper-
polarized. A rise in plasma glucose leads to the entry of more
glucose into beta cells by facilitated diffusion through GLUT1
carriers. The glucose undergoes aerobic respiration, leading
to an increase in ATP. This causes closing of the ATP-gated
K^1 channels in the plasma membrane, producing a depolariza-
tion that can reach a threshold and produce an action potential.
At the peak of the action potential, Ca^2 1 channels open in the
plasma membrane and the Ca^2 1 that enters the cell at this time
stimulates the exocytosis of insulin ( fig. 19.8 ).
A rise in plasma glucose thus leads to a rise in insulin secre-
tion; at the same time, it inhibits the secretion of glucagon from
the alpha cells of the islets. Because insulin lowers the plasma
glucose concentration (by stimulating the cellular uptake of
plasma glucose), and glucagon acts antagonistically to raise
the plasma glucose (by stimulating glycogenolysis in the liver),
these changes in insulin and glucagon secretion help maintain
homeostasis during the absorption of a carbohydrate meal.

Figure 19.8 Regulation of insulin secretion. (1) A

rise in blood glucose causes more glucose to enter the beta

cells of the islets of Langerhans, resulting in (2) an increased

production of ATP. (3) This closes K^1 channels, so that K^1 ions

cannot leave the cell. (4) This produces a depolarization, which

(5) opens voltage-gated Ca^2 1 channels, permitting the entry of

Ca^2 1 into the cytoplasm. (6) Ca^2 1 stimulates intracellular vesicles

containing insulin to fuse with the plasma membrane and release

insulin by exocytosis.

훃 cell

Stimulus

Blood glucose

Glucose

GLUT2

Vesicle

containing

insulin

Closes K+

channels

Oxidative

phosphorylation

CO 2 + H 2 O

Depolarization

Fusion and

exocytosis

of vesicles

Opens

voltage-

gated Ca2+

channels

AT P

Ratio of ATP to ADP

Glucose 6–P

Krebs

cycle Glycolysis

Ca2+

Ca2+

Insulin

Response

Insulin

secreted

+

2

1

3

4

(^56)