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