Human Physiology, 14th edition (2016)

Endocrine Glands 329

effects are achieved by a mechanism of action that is quite com-

plex, and in some ways still not completely understood. Nev-

ertheless, it is known that insulin’s mechanism of action bears

similarities to the mechanism of action of other regulatory mole-

cules known as growth factors. These growth factors, including

epidermal growth factor (EGF), platelet-derived growth factor

(PDGF), and insulin-like growth factors (IGFs), are autocrine

regulators (described at the end of this chapter).

In the case of insulin and the growth factors, the recep-

tor protein is located in the plasma membrane and is itself an

enzyme known as a tyrosine kinase. A kinase is an enzyme

that adds phosphate groups to proteins, and a tyrosine kinase

specifically adds these phosphate groups to the amino acid

tyrosine within the proteins.

binds to a protein called calmodulin. Once Ca^2 1 binds to
calmodulin, the now-active calmodulin in turn activates spe-
cific protein kinase enzymes (those that add phosphate groups
to proteins) that modify the actions of other enzymes in the
cell ( fig.  11.10 ). Activation of specific calmodulin-dependent
enzymes is analogous to the activation of enzymes by cAMP-
dependent protein kinase. The steps of the Ca^2 1 second-
messenger system are summarized in table 11.5.

Tyrosine Kinase Second-Messenger System

Insulin promotes glucose and amino acid transport and stimu-
lates glycogen, fat, and protein synthesis in its target organs—
primarily the liver, skeletal muscles, and adipose tissue. These

Figure 11.9 The phospholipase

C–Ca^2 1 second-messenger

system. (1) The hormone binds to its

receptor in the plasma membrane of its

target cell, (2) causing the dissociation

of G-proteins. (3) A G-protein subunit

travels through the plasma membrane

and activates phospholipase C,

which catalyzes the breakdown of a

particular membrane phospholipid into

DAG (diacylglycerol) and IP 3 (inositol

triphosphate). (4) IP 3 enters the cytoplasm

and binds to receptors in the endoplasmic

reticulum, causing the release of stored

Ca^2 1. The Ca^2 1 then diffuses into the

cytoplasm, where it acts as a second

messenger to promote the hormonal

effects in the target cell.

Receptor

protein Hormone

G-proteins

Cytoplasm Ca2+

Ca2+

Ca2+

Ca2+ Ca2+Ca2+

Ca2+ Ca2+

Ca2+

Phospholipase C

Endoplasmic

reticulum

Plasma

membrane

IP 3

DAG

1

2

4

3

Figure 11.10 Epinephrine

uses two second-messenger

systems. This is shown by the action

of epinephrine on a liver cell. (1) Binding

of epinephrine to beta-adrenergic

receptors activates adenylate cyclase

and leads to the production of cAMP,

which (2) activates a protein kinase.

(3) Binding of epinephrine to alpha-

adrenergic receptors leads to a rise in the

cytoplasmic Ca^2 1 concentration, which

(4) activates calmodulin. Calmodulin then

activates a protein kinase, which, like the

protein kinase activated by cAMP,

(5) alters enzyme activity so that

glycogen is converted to glucose

6-phosphate. (6) The phosphate group is

removed by another enzyme, so that the

liver cell secretes free glucose into the

blood in response to epinephrine.

1

2

5

6

4

3

Liver cell

Ca2+

Calmodulin Ca2+

Active protein

kinase

Active

protein

kinase

cAMP

Adenylate

cyclase

AT P

Glycogen

Glucose 1-phosphate

Glucose 6-phosphate Free glucose

Beta-adrenergic
effect of
epinephrine

Alpha-adrenergic

effect of

epinephrine