Human Physiology, 14th edition (2016)

680 Chapter 19

glucagon secretion, promote gluconeogenesis —the forma-
tion of glucose from noncarbohydrate molecules. Low insulin
allows the release of amino acids from skeletal muscles, while
glucagon and cortisol (an adrenal hormone) stimulate the pro-
duction of enzymes in the liver that convert amino acids to
pyruvic acid and pyruvic acid into glucose. During prolonged
fasting and exercise, gluconeogenesis in the liver using amino
acids from muscles may be the only source of blood glucose.
The secretion of glucose from the liver during fasting com-
pensates for the low blood glucose concentrations and helps to
provide the brain with the glucose that it needs. But because insu-
lin secretion is low during fasting, skeletal muscles cannot utilize
blood glucose as an energy source. Instead, skeletal muscles—as
well as the heart, liver, and kidneys—use free fatty acids as their
major source of fuel. This helps to “spare” glucose for the brain.
The free fatty acids are made available by the action of glu-
cagon. In the presence of low insulin levels, glucagon activates
an enzyme in adipose cells called hormone-sensitive lipase. This
enzyme catalyzes the hydrolysis of stored triglycerides and the
release of free fatty acids and glycerol into the blood. Glucagon
also activates enzymes in the liver that convert some of these
fatty acids into ketone bodies, which are secreted into the blood
( fig.  19.9 ). Several organs in the body can use ketone bodies, as
well as fatty acids, as a source of acetyl CoA in aerobic respiration.
Through the stimulation of lipolysis (the breakdown of
fat) and ketogenesis (the formation of ketone bodies), the high
glucagon and low insulin levels during fasting provide circulat-
ing energy substrates for use by the muscles, liver, and other
organs. Through liver glycogenolysis and gluconeogenesis,
these hormonal changes help to provide adequate levels of

Fasting (↓ insulin, ↑ glucagon)

Glycogen Glucose

6-phosphate

Glucose

Pyruvic acid

Acetyl CoA

Ketone bodies

Liver

Skeletal muscle

Adipose tissue

Glucose

Amino

acids

Ketone

bodies

Fatty

acids

Figure 19.9 Catabolism
during fasting. Increased glucagon
secretion and decreased insulin
secretion during fasting favors
catabolism. These hormonal changes
promote the release of glucose, fatty
acids, ketone bodies, and amino
acids into the blood.
Notice that the liver
secretes glucose that is
derived both from the
breakdown of liver glycogen
and from the conversion of
amino acids in gluconeogenesis.

| CHECKPOINT

8a. Describe how the secretions of insulin and glucagon

change during periods of absorption and periods of

fasting. How are these changes in hormone secretion

produced?

8b. Explain how the synthesis of fat in adipose cells

is regulated by insulin. Also, explain how fat

metabolism is regulated by insulin and glucagon

during periods of absorption and fasting.

8c. Define the following terms: glycogenolysis,

gluconeogenesis, and ketogenesis. How do insulin

and glucagon affect each of these processes during

periods of absorption and fasting?

9. Describe two pathways used by the liver to produce
   glucose for secretion into the blood. Why can’t
   skeletal muscles secrete glucose into the blood?

blood glucose to sustain the metabolism of the brain. By serv-

ing as energy substrates for the muscles and other organs, the

free fatty acids and ketone bodies spare blood glucose for use

by the brain. Free fatty acids also reduce the activity of gly-

colytic enzymes in muscles, hindering the ability of muscles

to utilize glucose for energy so that more is available for the

brain. These changes, together with the glucose provided by

glycogenolysis and gluconeogenesis promoted by high gluca-

gon/ low insulin levels, sustain body metabolism during fasting

(and exercise) conditions ( fig. 19.10 ).